System, method and apparatus for evaluating tissue temperature

ABSTRACT

Method, system and apparatus for monitoring target tissue temperatures wherein temperature sensors are configured as passive resonant circuits each with a unique resonating signature at monitoring temperatures extending below a select temperature setpoint. The resonant circuits are configured with an inductor component formed of windings about a ferrite core having a Curie temperature characteristic corresponding with a desired temperature setpoint. By selecting inductor winding turns and capacitance values, unique resonant center frequencies are detectable. Temperature monitoring can be carried out with implants at lower threshold and upper limit temperature responses. Additionally, the lower threshold sensors may be combined with auto-regulated heater implants having Curie transitions at upper temperature limits.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a division of application Ser. No. 10/733,970, filedDec. 11, 2003, now U.S. Pat. No. 7,048,756; and claims the benefit ofU.S. Provisional Application No. 60/466,223, filed Apr. 28, 2003; and isa continuation-in-part of U.S. application Ser. No. 10/246,347, filedSep. 18, 2002, now U.S. Pat. No. 6,993,394; which is a continuation ofU.S. patent application Ser. No. 10/201,363 filed Jul. 23, 2002, nowabandoned; claiming the benefit of U.S. Provisional Application No.60/349,593 filed Jan. 18, 2002.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

Not applicable.

BACKGROUND OF THE INVENTION

A beneficial response elicited by a heating of neoplastic tissue wasreported by investigators in 1971. See the following publications inthis regard:

-   -   (1) Muckle, et al., “The Selective Inhibitory Effect of        Hyperthermia on the Metabolism and Growth of Malignant Cells”        Brit J. of Cancer 25:771-778(1971).    -   (2) Castagna, et al., “Studies on the Inhibition by Ethionine of        Aminoazo Dye Carcinogenesis in Rat Liver.” Cancer Research        32:1960-1965 (1972).        While deemed beneficial, applications of such thermotherapy        initially were constrained to external surface heating. When        external applications have been employed the resultant body        structure heating has been described as having been uncontrolled        in thermal localization resulting in temperature elevation of        the whole body. Employment of diathermy has been reported with a        resultant non-destructive inhibitory reaction. In general, no        consensus by investigators as to the efficacy of thermotherapy        with respect to tumor was present as late as the mid 1970s. See        generally:    -   (3) Strom, et al., “The Biochemical Mechanism of Selective Heat        Sensitivity of Cancer Cells—IV. Inhibition of RNA Synthesis.”        Europ. J. Cancer 9:103-112(1973).    -   (4) Ziet. fur Naturforschung 8, 6: 359.    -   (5) R. A. Holman, Letter “Hyperthermia and Cancer”, Lancet, pp.        1027-1029 (May 3, 1975).

Notwithstanding a straightforward need for more effective techniques inthe confinement of thermotherapy to localized internally located targettissue regions, investigators have established that tumor cells may bephysiologically inhibited by elevating their temperatures above normalbody temperature, for example, 37° C. for one major population, to arange exceeding about 40° C. The compromising but beneficial resultsfurther are predicated upon that quantum of thermal exposure achieved,based upon the time interval of controlled heat application. Thus,effective thermotherapies are characterized by an applied quantum ofthermal energy established within a restrictive tissue periphery orvolume of application with an accurately controlled temperature over aneffective component of time.

One modality of thermotherapy is termed “hyperthermia” therapy, anapproach to thermal treatment at temperatures elevated within somewhatnarrow confines above normal body temperature. For instance, theelevation above a normal body temperature of 37° C. typically will fallwithin a range of 42° C. to 45° C. While higher temperature therapieshave been described, hyperthermia therapy conventionally looks toaffecting tissue to the beneficial effect of, for instance, negatingneoplastic development, while avoiding denaturization, i.e., cell deathor necrosis. It follows that an embracing of this therapeutic modalitycalls for the application of thermal control over specific tissuevolumes.

Confinement of thermotherapy to a neoplasm-suspect target tissue volumeinternally disposed within the body without a generation of damage tohealthy surrounding tissue has been considered problematic and thus thesubject of diverse investigation. Experience in this field has revealedthat achieving a controlled, thermo-therapeutic level of heat throughouta targeted tissue volume is difficult. In general, the distribution ofinduced heat across such tissue volumes can exhibit substantialvariations. Vascularity and densities of heterogeneous tissues mayimpose such variations. For instance, the cooling properties of bloodflow complicate the maintenance of a desired thermal dose at the targetvolume. A variety of approaches toward intra-body localized heatapplications have evolved. Such efforts generally have been based uponthe application of microwave energy (U.S. Pat. No. 4,138,998); theapplication of acoustic wave-based systems (ultrasound); the applicationof electric fields at RF frequencies (direct RF) from transmittingantenna arrays including an application subset utilizing inductivesystems driven at relatively lower frequencies within the RF realm, andthe utilization of infra red heaters.

Ultrasound is considered to be an acoustic wave above the normal rangeof human hearing, i.e., above about 20,000 Hertz. When employedclinically for thermo-therapeutic as well as diagnostic purposes,ultrasound system configurations perform in recognition of the acousticimpedance of investigated tissue. Acoustic impedance is the resistanceto wave propagation through tissue, for example, due to absorbance,reflectance or molecularly induced scattering. Accordingly, the subjecttissue volume will absorb some of the energy from the ultrasound wavespropagated through it and the kinetic energy associated with the energyabsorbed is converted into thermal energy to thus raise tissuetemperature. See generally U.S. Pat. No. 6,451,044. When implementingultrasound thermotherapy systems, careful control is called for toassure that minimum threshold tissue temperatures are reached and thatmaximum tissue temperature limits are not exceeded. Heretofore,temperature monitoring generally has been carried out by percutaneouslyinjecting or otherwise inserting tethered temperature sensors such asthermocouples or thermistors into the targeted tissue region. Insertionof a tethered thermocouple may be accomplished by first inserting ahypodermic needle, then inserting a catheter through the needle with thesensor at its tip, whereupon the needle is withdrawn. Where hyperthermiatherapy or heat induced immunotherapy are carried out, maintenance ofrelatively narrow temperature targets is sought, calling for a highlevel of control. For these thermotherapies, typically multiple therapysessions are required, thus the generally undesirable injection orinsertion of temperature sensors must be carried out for each of whatmay be many treatment sessions.

One approach has been advanced for ultrasound-based thermotherapy. Inthat approach, thermal localization is achieved by developingconstructive wave interference with phased array-based wave guideapplicators mounted to extend around the patient (see U.S. Pat. Nos.5,251,645 and 4,798,215).

The microwave band generally is considered to extend from about 900 Mhz.Clinical studies have established that thermotherapy systems can beimplemented with microwave radiating devices. Early endeavors utilizingmicrowave-based hyperthermia treatment evidenced difficulties in heatingtarget tissue volumes at adequate depth while preventing surroundingsuperficial healthy tissue from incurring pain or damage due to hotspots exhibiting temperatures greater than about 44-45° C. However,later developments using adaptive phased array technology has indicatedthat relatively deeply located target tissues can be heated tothermotherapeutic temperatures without inducing the earlierdifficulties. See generally the following publication:

-   -   (6) Fenn, et al, “An Adaptive Microwave Phased Array For        Targeted Heating Of Deep Tumors In Intact Breast: Animal Studies        Results” Int. J. Hyperthermia, Vol. 15, No. 1, pp 45-61 (1999).

Inductively-based approaches to thermotherapy systems have receivedimportant attention by investigators. The coil transmitted outputs ofthese systems generally are focused for field convergence toward thetarget tissue volume and the resultant, internally thermally affectedtissue region has been monitored in situ by thermo-responsive sensorssuch as rod-mounted thermocouples and thermistors. Those tethered heatsensors are inserted percutaneously into the target tissue region, beingcoupled by extra-body electrical leads extending to connections withtemperature monitoring readouts. As before, the invasiveness of themonitoring electrical leads extending into the patients' body for thisprocedure has been considered undesirable. This particularly holds whererepetitive but time-spaced procedures are called for, or the therapeuticmodality is employed in thermally treating tumor within the brain.

The radio (RF) spectrum is defined as extending from the audio range toabout 300,000 MHz. However direct RF thermotherapy has been described inconjunction with the 80 MHz to 110 MHz range.

Another approach is described as performing as a focused radiofrequency/microwave region system, the election between these spectralregions being determined with respect to the depth of the target tissue.See: htp://www.bsdme.com/.

Efforts to regionalize or confine therapeutic tissue heating topredefined borders or volumetric peripheries have included procedureswherein small wire or iron-containing crystals (U.S. Pat. No. 4,323,056)are implanted strategically within the tissue region of interest.Implantation is achieved with an adapted syringe instrumentality.Electromagnetic fields then are introduced to the region to inductivelyheat the implanted radiative-responsive heater components and thus evokea more regionally controlled form of thermotherapy. In one suchapproach, ferromagnetic thermoseeds have been employed which exhibitCurie temperature values somewhat falling within the desired temperaturerange for an elected thermotherapy. This achieves a form of selfregulation by operation of the system about those Curie transitions. Forinstance, as radiative inductive excitation drives the thermoseeds totemperatures to within the permeability based state change levelsassociated with attainment of a Curie temperature range, the thermoseedsbecome immune to further application of external excitation energy. (Seegenerally U.S. Pat. No. 5,429,583). Unfortunately, the Curie transitiontemperature range of the thermoseeds is relatively broad with respect tothe desired or target temperature. This expanded Curie transition rangeis, in part, the result of the presence of the ferrite-based seedswithin relatively strong electromagnetic fields. The result is asomewhat broad and poor regulation temperature band which may amount 10°or more. As a consequence, the auto-regulated devices are constrained touses inducing tissue necrosis or ablation, as opposed to uses withtemperatures controlled for hyperthermia therapies.

See generally:

-   -   (7) Brezovich, et al., “Practical Aspects of Ferromagnetic        Thermoseed Hyperthermia.” Radiologic Clinics of North America,        27: 589-682 (1989).    -   (8) Haider, et al., “Power Absorption in Ferromagnetic Implants        from Radio Frequency Magnetic Fields and the Problem of        Optimization.” IEEE Transactions On Microwave Theory And        Techniques, 39: 1817-1827 (1991).    -   (9) Matsuki et al., “An Optimum Design Of A Soft Heating System        For Local Hyperthermia” IEEE Transactions On Magnetics, 23(5):        2440-2442, (September 1987).

Thermotherapeutic approaches designed to avoid the subcutaneousinsertion of one or more temperature sensors have looked to the controlof heating using modeling methodology. These approximating modelingmethods are subject to substantial error due to differences or vagariesexhibited by the heterogeneous tissue of any given patient. Suchdifferences may be due to variations in vascularity, as well as thegradual metamorphosis of a tumor mass. The latter aspect may involvesomewhat pronounced variations in tissue physiologic characteristicssuch as density. See generally the following publication:

-   -   (10) Arkin, H. et al., “Recent Development In Modeling Heat        Transfer in Blood Perfused Tissue.” IEEE Transactions on        Bio-Medical Engineering, 41 (2): 97-107 (1994).

Some aspects of thermotherapy have been employed as an adjunct to theuse of chemotherapeutic agents in the treatment of tumor. Because of theprecarious blood supply or vascularity and of the high interstitialfluid presence, such agents may not be effectively delivered to achievea 100% cell necrosis. Further the tumor vessel wall may pose a barrierto such agents, and resultant non-specific delivery may lead tosignificant systemic toxicities. Studies have addressed these aspects ofchemotherapy, for instance, by the utilization of liposomes toencapsulate the chemotherapeutic agents to achieve preferential deliveryto the tumor. However the efficiencies of such delivery approaches havebeen somewhat modest. Clinically, hyperthermia therapy has been employedas a form of adjunct therapy to improve the efficiency of moreconventional modalities such as radiation therapy and chemotherapy. Forthe latter applications the thermal aspect has been used to augmentbloodstream borne release agents or liposome introduction to the tumorsite. Hyperthermia approaches have been shown to trigger agent releasefrom certain liposomes, making it possible to release liposome contentsat a heated site (U.S. Pat. Nos. 5,490,840; 5,810,888). For any suchthermotherapeutic application, an accurate temperature control at thesitus of the release is mandated. See the following publications:

-   -   (11) Kong, et al., “Efficacy of Lipsomes and Hyperthermia in a        Human Tumor Xenograft Model: Importance of Triggered Drug        Release.” Cancer Research, 60: 6950-6957 (2000).    -   (12) Chung, J. E., et al., “Thermo-Responsive Drug Delivery From        Polymeric Micelles Using Block Co-Polymers of Poly        (N-isopropylacrylamide-b-butylmethacrylate) and Poly        (butylmethacrylate), Journal of Controlled Release        (Netherlands), 62(2): 115-127 (Nov. 1, 1999).

Hyperthermia when used in conjunction with radiation treatment ofmalignant disease has been demonstrated as beneficial for destroying aspecific tumor site. Clinical data has evolved demonstrating an improvedefficacy associated with combined radiation and hyperthermia treatmentsas compared to radiation therapy alone. Such multimodal therapy conceptsalso have been extended to a combination of hyperthermia treatment withboth radiation treatment and chemotherapy (radiochemotherapy). Seegenerally:

-   -   (13) Falk et al., “Hyperthermia In Oncology” Int. J.        Hyperthermia, 17: 1-18 (2001).

Biological mechanisms at the levels of single cells activated by heatbecame the subject of scientific interest in the early 1960s asconsequence of the apparently inadvertent temperature elevation of anincubator containing Drosophila melanogaster (fruit flies). Thesecreatures, upon being heat shocked, showed the characteristic puffsindicative of transcriptional activity and discrete loci. See thefollowing publication:

-   -   (14) Ritossa, “A New Puffing Pattern Induced By Temperature        Shock and DNP in Drosophila.” Experientia, 18: 571-573 (1962).        These heat shock loci encoding the heat shock proteins (HSPs),        became models for the study of transcriptional regulation,        stress response and evolution. The expression of HSPs may not        only be induced by heat shock, but also by other mechanisms such        as glucose deprivation and stress. Early recognized attributes        of heat shock proteins resided in their reaction to        physiologically support or reinvigorate heat damaged tissue.        (See U.S. Pat. No. 5,197,940). Perforce, this would appear to        militate against the basic function of thermotherapy when used        to carry out the denaturization of neoplastic tissue. However,        heat shock phenomena exhibit a beneficial attribute where the        thermal aspects of their application can be adequately        controlled. In this regard, evidence that HSPs, possess unique        properties that permit their use in generating specific immune        responses against cancers and infectious agents has been        uncovered. Additionally, such properties have been subjects of        investigation with respect to boney tissue repair, transplants        and other therapies. See generally the following publications:    -   (15) Anderson et al., “Heat, Heat Shock, Heat Shock Protein and        Death: A Central Link in Innate and Adoptive Immune Responses.”        Immunology Letters, 74: 35-39 (2000).    -   (16) Srivastava, et al, “Heat Shock Proteins Come of Age:        Primitive Functions Acquire New Role In an Adaptive World.”        Immunity, 8(6): 657-665 (1998).

Beneficial thermal compromization of target tissue volumes is notentirely associated with HSP based treatments for neoplastic tissue andother applications, for instance, having been studied in connection withcertain aspects of angioplasty. Catheter-based angioplasty was firstintentionally employed in 1964 for providing a transluminal dilation ofa stenosis of an adductor hiatus with vascular disease. Balloonangioplasty of peripheral arteries followed with cautious approaches toits implementation to the dilation of stenotic segments of coronaryarteries. By 1977 the first successful percutaneous transluminalcoronary angioplasty (PTCA) was carried out. While, at the time,representing a highly promising approach to the treatment of anginapectoris, subsequent experience uncovered post-procedural complications.While PTCA had been observed to be effective in 90% or more of thesubject procedures, acute reclosure, was observed to occur inapproximately 5% of the patients. Stenosis was observed to occur in somepatients within a period of a few weeks of the dilational procedure andrestenosis was observed to occur in 15% to 43% of cases within sixmonths of angioplasty. See generally:

-   -   (17) Kaplan, et al., “Healing After Arterial Dilatation with        Radiofrequency Thermal and Non-Thermal Balloon Angioplasty        Systems.” Journal of Investigative Surgery, 6: 33-52 (1993).

In general, the remedy for immediate luminal collapse has been a resortto urgent or emergency coronary bypass graft surgery. Thus, the originalprocedural benefits attributed to PTCA were offset by the need toprovide contemporaneous standby operating room facilities and surgicalpersonnel. A variety of modalities have been introduced to avoid postPTCA collapse, including heated balloon-based therapy, (Kaplan, et al.,supra) the most predominate being the placement of a stent extendingintra-luminally across the dilational situs. Such stents currently areused in approximately 80% to 90% of all interventional cardiologyprocedures. While effective to maintain or stabilize intra-luminaldilation against the need for emergency bypass procedures, the stentsare subject to the subsequent development of in-stent stenosis orrestenosis (ISR). See generally:

-   -   (18) Holmes, Jr., “In-Stent Restenosis.” Reviews in        Cardiovascular Medicine, 2: 115-119 (2001).        Debulking of the stenotic buildup has been evaluated using laser        technology; rotational atherectomy; directional coronary        atherectomy; dualistic stent interaction (U.S. Pat. No.        6,165,209); repeated balloon implemented dilation, the        application of catheter introduced heat to the stent region        (U.S. Pat. No. 6,319,251); the catheter-borne delivery of soft        x-rays to the treated segment, sonotherapy; light activation;        local arterial wall alcohol injection; and ultrasound heating of        a stent formed of an ultrasound absorptive material (U.S. Pat.        No. 6,451,044).

See additionally the following publications with respect to atherectomyfor therapeutically confronting restenosis:

-   -   (19) Bowerman, et al., “Disruption of Coronary Stent During        Artherectomy for Restenosis.” Catherization and Cardiovascular        Diagnosis, 24: 248-251 (1991).    -   (20) Meyer, et al., “Stent Wire Cutting During Coronary        Directional Atherectomy.” Clin. Cardiol, 16: 450-452 (1993).

In each such approach, additional percutaneous intervention is calledfor. See generally the following publication:

-   -   (21) Vliestra and Holmes, Jr., Percutaneous Transluminal        Coronary Angioplasty Philadelphia: F. A. Davis Co. (Mayo        Foundation) (1987).

Other approaches have been proposed including the application ofelectrical lead introduced electrical or RF applied energy to metallicstents, (U.S. Pat. No. 5,078,736); the incorporation of radioisotopeswith the stents (U.S. Pat. Nos. 6,187,037; 6,192,095); and resort todrug releasing stents (U.S. Pat. No. 6,206,916 B1). While non-invasivecontrol of ISR has been the subject of continued study, the developmentof a necessarily precise non-invasively derived control over it hasremained an elusive goal.

Another application of hyperthermia is in orthopedics, as a means tostimulate bone growth and fracture healing. There are several FDAapproved devices for stimulation of bone growth or healing, each withlimitations and side effects. Therapies include invasive electricalstimulation, electromagnetic fields, and ultrasound stimulation. Decadesold research has claimed a stimulation of bone growth by a mild increasein temperature of the boney tissue. Previous researchers have used suchmethods as inductive heating of implanted metal plates, or heating coilswrapped around the bone. The utility of these methods is limited by theinvasive nature of the surgery needed to implant the heating elementsand the inability to closely control tissue temperature. Moreover,therapeutic benefits have been inconsistent between different studiesand experimental protocols. For a summary of past work, see generally:

-   -   (22) Wootton, R. Jennings, P., King-Underwood, C., and Wood, S.        J., “The Effect of Intermittent local Heating on Fracture        Healing in the Distal Tibia of the Rabbit.” International        Orthopedics, 14: 189-193 (1990).

A number of protocols have demonstrated a beneficial effect ofhyperthermia on bone healing. Several studies indicate temperatureaffects bone growth and remodeling after injury. Hyperthermia may bothimprove blood supply and stimulate bone metabolism and have a directeffect on bone-forming cells by inducing heat shock proteins or othercellular proteins. In one experiment, rabbit femurs were injured bydrilling and insertion of a catheter. Hyperthermia treatments were givenat four-day intervals for 2-3 weeks using focused microwave radiation.Bones which had suffered an insult as a result of the experimentalprocedure showed a greater density of osteocytes and increased bone masswhen treated with hyperthermia. Injured bones treated with hyperthermiashowed completely ossified calluses after two weeks, while theseprocesses normally take four weeks in untreated injuries. One problemwith microwave heating of bone mass is the difficulty in predicting heatdistribution patterns and maintaining the target tissue within theappropriate heat range.

When tissue is heated at too high of temperature, there can beirreversible cytotoxic effects which could damage bone and othertissues, including osteogenic cells, rather than induce healing. Certainstudies have shown that induction of mild heat shock promotes bonegrowth, while more severe heat shock inhibits bone growth. Therefore,control and monitoring of the temperature of the targeted bone tissue isimperative to achieve therapeutic benefit and avoid tissue damage.

See additionally the following publications with respect to hyperthermiafor therapeutically promoting osteogenesis:

-   -   (23) Leon, et al., “Effects of Hyperthermia on Bone. II. Heating        of Bone in vivo and Stimulation of Bone Growth.” Int. J.        Hyperthermia 9: 77-87 (1993).    -   (24) Shui et al., “Mild heat Shock Induces Proliferation,        Alkaline Phosphatase Activity, and Mineralization in Human Bone        Marrow Stromal Cells and Mg-63 Cells In Vitro.” Journal of Bone        and Mineral Research 16: 731-741 (2001).    -   (25) Huang, C.-C., Chang, W. H., and Liu, H.-C. “Study on the        Mechanism of Enhancing Callus Formation of Fracture by        Ultrasonic Stimulation and Microwave Hyperthermia.” Biomed. Eng.        Appl. Basis Comm. 10: 14-17 (1998).

Existing protocols for therapeutically promoting osteogenesis arelimited by the invasive nature and concomitant potential for infectionfor instance with tethered electrical stimulators; poor temperaturecontrol, and potential for tissue injury or reduced therapeutic benefit,for instance with microwave heating or other induced electromagneticfields; difficulty in effectively applying therapy to the injured bonebecause of targeting difficulties or low patient compliance withprescribed repetitive therapy.

The host immune system can be activated against infectious disease byheat shock protein chaperoned peptides in a manner similar to the effectseen against metastatic tumors. Heat shock proteins chaperoning peptidesderived from both viral and bacterial pathogens have been shown to beeffective at creating immunity against the infectious agent. Forinfectious agents for which efficacious vaccines are not currentlyavailable (especially for intracellular pathogens e.g. viruses,Mycobacterium tuberculosis or Plasmodium) HSP chaperoned peptides may beuseful for the development of novel vaccines. It is expected thatpurified HSP chaperoned peptides (e.g. gp96 complexes) used as vaccinesfor diseases caused by highly polymorphic infectious agents would beless effective against genetically distinct pathogen populations. For asummary of past work on HSP vaccines against infectious agents, seegenerally:

-   -   (26) Neiland, Thomas J. F., M. C. Agnes A. Tan, Monique        Monnee-van Muijen, Frits Koning, Ada M. Kruisbeek, and Grada M.        van Bleek, “Isolation of an immunodonminant viral peptide that        is endogenously bound to stress protein gp96/GRP94.” Proc. Nat'l        Acad. Sci. USA, 93: 6135-6139 (1996).    -   (27) Heikema, A., Agsteribbe, E., Wilschut, J., Huckriede, A.,        “Generation of heat shock protein-based vaccines by        intracellular loading of gp96 with antigenic peptides.”        Immunology Letters, 57: 69-74 (1997).    -   (28) Zugel, U., Sponaas, A. M., Neckermann, J., Schoel, B., and        Kaufmann, S. H. E., “gp96-Peptide Vaccination of Mice Against        Intracellular Bacteria.” Infection and Immunity, 69: 4164-4167        (2001).    -   (29) Zugel, U., and Kaufmann, S. H. E., “Role of Heat Shock        Proteins in Protection from and Pathogenesis of Infectious        Diseases.” Clinical Microbiology Reviews, 12: 19-39 (1999).

In commonly owned co-pending application for U.S. patent Ser. No.10/246,347, filed Sep. 18, 2002 and entitled “System, Method andApparatus for Localized Heating of Tissue”, an approach to accuratelycarrying out an in situ elevation of the temperature of a target tissuevolume is presented. Accuracy is achieved using untethered temperaturesensor implants formed of ferromagnetic material which experiences anabrupt magnetic permeability state change within a very narrowtemperature range. Temperature sensing is carried out by monitoring avery low level magnetic field extending through the position of theimplant. For instance, the earth's magnetic field may be employed. Whereinductively based heating is utilized, non-magnetic heaters may beimplanted with the sensors and sensing is carried out intermittently inthe absence of the inductably derived magnetic field.

BRIEF SUMMARY OF THE INVENTION

The present invention is addressed to method, system and apparatus foraccurately evaluating a temperature related physical parameter withinthe body of a patient. Accurate temperature measurement is achievedthrough the use of one or more tetherless temperature sensorsstrategically located within the body and configured with a passiveresonant circuit. These passive circuits respond to an extra bodyapplied excitation electromagnetic field by resonating at anidentifiable unique resonant center frequency. In one embodiment, theresonant circuit based sensors are configured with a capacitor and aseries coupled inductor formed with a winding disposed about a ferritecore. That ferrite core is formulated to exhibit a somewhat sharppermeability state change or transition at a Curie temperaturecorresponding with a desired temperature setpoint. With the arrangement,upon being excited by an applied excitation burst, the sensor will ringor resonate at its unique, signature resonant center frequency when atmonitor temperatures below the involved Curie temperature. As the sensorwitnesses monitoring temperatures approaching the Curie temperaturedefined setpoint the intensity of its unique resonant center frequencydecreases, an aspect which may be taken advantage of from a temperaturecontrol standpoint. However, when the Curie or target temperature isreached, the relative permeability of the sensor's ferrite core dropssharply toward a unity value to, in turn, cause a sharp drop in thereluctance of the associated inductor coil causing the resonantfrequency of the device to shift substantially upward in value. Thisshift is to an off-scale value. In effect, the signature outputdisappears. As the sensors resonate in response to excitation, thedetector components of the associated interrogation system are capableof sensing all of the resonating devices, whereupon the sensed signalsare digitized, averaged and analyzed to identify each sensor by itsunique resonant center frequency, if at the noted monitor temperatures.Such analysis may be carried out using a Fourier transform-typeapproach. Because the unique resonant center frequency remains stable asthe temperatures witnessed by the sensors, approach or transition towardthe Curie temperature-based setpoint, the amplitude of the Fouriertransform signal will diminish and the system has the capability ofpredicting the arrival of the Curie based setpoint temperature. Thermalovershoot can thus be more accurately accommodated for.

The unique resonant center frequencies of the sensors are readilyestablished by adjusting the value of inductance and/or capacitance ofthe passive resonant circuits. In general, the unique resonant centerfrequencies are developed within a frequency band ranging from about 100kHz to about 2 MHz. Accordingly, a substantial range of sensorsignatures are available to the system.

A feature of the system and method of the invention is concerned with atypical patient management regimen wherein a relatively substantialrepetition of thermotherapeutic procedures is called for. The sensorsremain in position with respect to the target tissue volume and may, inthis regard, be fashioned with anchors for the purpose of migrationavoidance. Where a succession of treatments is involved, not only isthere no requirement to re-install sensors, but also, the alignment ofexcitation and sensing antennae as well as heating unit outputorientations essentially are simply repeated. Another aspect of thisfeature resides in the utilization of the pre-implanted sensors as aconventional tumor situs marker for subsequent patient evaluationimaging procedures.

In one embodiment of the invention one or more of the sensor implantsare configured to exhibit Curie transitions at a lower thresholdsetpoint temperature, while an additional one or more are configured toexhibit Curie transitions at an upper limit higher setpoint temperature.Thus, the practitioner will be apprised of the target tissue volumereaching that minimum temperature adequately for therapy, as well as ofany temperature excursions above the upper limit. Where such thermalexcursions occur, the heating unit involved may be adjusted, forexample, in terms of power level as well as component positioning.

Those sensor implants configured to identify attainment of a lowerthreshold temperature setpoint may be combined with ferrite coreimplemented auto-regulating heater implants having Curie transitions atan upper limit higher temperature setpoint. This particular combinationwill be beneficial where the thermotherapy temperature levels involvedwill approach apoptosis or necrosis levels, as well as for thepreviously mentioned hyperthermia therapy administered in the rangebetween approximately 40° C. and 45° C.

The instant method has broad application to thermotherapy endeavorsincluding an in vivo induction of heat shock proteins, a procedurehaving important utility in the treatment of cancer, infectious diseasesand other therapies. As another modality, one or more of the sensors iscombined with an intra-luminal stent and when so combined and implanted,permit a non-invasive repeatable and accurate hyperthermia therapy forstenosis/restenosis.

The implant control heating approach of the invention also may beapplied to the field of orthopedics. In this regard, the sensorcomponents may be combined in intimate thermal exchange relationshipwith non-magnetic metal bone support devices implanted with bony tissue.The setpoint temperature elected for such modality is selected toenhance the repair of the mending bony tissue.

Implant based controlled in vivo heating according to the precepts ofthe invention also may be employed as a vehicle for inducing immunityagainst or for the treatment of diseases cause by infectious agents.

Other objects of the invention will, in part, be obvious and will, inpart appear hereinafter.

The invention, accordingly, comprises the method, system and apparatuspossessing the construction, combination of elements, arrangement ofparts and steps which are exemplified in the following detaileddescription.

For a fuller understanding of the nature and objects of the invention,reference should be made to the following detailed description taken inconnection with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a partial schematic view of a prior art approach to heating atarget tissue volume utilizing an auto-regulating heater implant;

FIG. 2 shows curves relating relative permeability with temperature forsensors employing ferromagnetic components;

FIG. 3 is a generalized semi-log curve illustrating the temporalrelationship between the duration of application of a given temperatureto tissue with the value of critical temperatures;

FIG. 4 illustrates a prior art approach to heating a targeted tissuevolume utilizing tethered heat sensors located within the target tissuevolume;

FIG. 5 shows curves relating relative permeability under low levelapplied magnetic field intensities and under high level applied magneticfield intensities;

FIG. 6 is a flowchart illustrating the production of ferrites;

FIG. 7 is an electrical schematic diagram of a passive resonant circuitconfigured to provide temperature sensing;

FIG. 8 is a schematic block diagram of a temperature monitoring systemaccording to the invention;

FIG. 9 is an oscillotrace showing a sensing response and associatedresonant frequency intensity;

FIG. 10A is a representation of the FFT relative amplitudes of foursensors at temperatures below a setpoint temperature;

FIG. 10B is a representation of the FFT relative amplitudes of thesensors of FIG. 10A during a Curie transition;

FIG. 10C is a set of curves relating the relative amplitudes of twosensors positioned with temperature sensors within a water bathenvironment;

FIGS. 11A-11F are electrical schematic diagrams showing an excitationcircuit employed with the system of the invention;

FIGS. 12A-12D are electrical schematic diagrams showing a detectorcircuit employed with the system of the invention;

FIG. 13 illustrates a block diagram of the interrogation system of theinvention;

FIG. 14 is a perspective view of a sensor according to the invention;

FIG. 14A is a sectional view of the sensor shown in FIG. 14 takenthrough the plane 14A-14A shown in FIG. 14B;

FIG. 14B is an end view of the sensor of FIG. 14A;

FIG. 14C is a top view of the sensor of FIG. 14A with components shownin phantom;

FIG. 15 is a perspective view of an auto-regulating heater implant;

FIG. 15A is a sectional view of the auto-regulating implant shown inFIG. 15;

FIG. 15B is an end view of the implant of FIG. 15A;

FIG. 15C is a perspective view of an implant according to the inventionwhich incorporates an anchor;

FIG. 15D is a sectional view of the auto-regulating heater of FIG. 15C;

FIG. 16 is a schematic and sectional view of an implant locatinginstrument which may be used with the implants of the invention showingthe instrument prior to releasing the implant in a targeted tissuevolume′

FIG. 17 is a schematic sectional view of the instrument of FIG. 16showing the delivery of a sensor implant into a targeted tissue volume;

FIG. 18 is a schematic view of a target tissue volume with a map form oflocation of temperature sensing implants;

FIG. 19 is a schematic representation of one embodiment of the system ofthe invention;

FIG. 20 is a graph schematically showing tissue temperature response tocontrolled extra body heating according to the invention;

FIGS. 21A-21G combine as labeled thereon to provide a flowchartillustrating a procedure and control carried out with the system of FIG.19;

FIG. 22 is a chart illustrating an intermittent heating andinterrogating feature of the system of the invention, the chart beingbroken along its timeline in the interest of clarity;

FIGS. 23A-23H combine as labeled thereon to provide a flowchartillustrating another intermittent procedure and control carried out withthe system represented in FIG. 19;

FIGS. 24A-24G combine as labeled thereon to provide a flowchartillustrating an intermittent procedure and control employing bothsensors and auto-regulating heaters as carried out with the systemrepresented in FIG. 19;

FIG. 25 is a schematic representation of another embodiment of thesystem of the invention;

FIGS. 26A-26J combine as labeled thereon to provide a flowchartillustrating the procedures and control carried out with the systemrepresented in FIG. 25;

FIG. 27 is a schematic sectional representation of a combined stent andtemperature sensor according to the invention embedded within a bloodvessel;

FIG. 28 is a sectional view taken through the plan 28-28 in FIG. 27;

FIG. 29 is a sectional schematic view of a stent according to theinvention incorporating a heat activated release agent coating and beingshown embedded within a blood vessel;

FIG. 30 is a sectional view taken through the plane 30-30 in FIG. 29;

FIG. 31 is a schematic sectional view of another stent embodimentaccording to the invention, the device being shown embedded within ablood vessel;

FIG. 32 is a sectional view taken through the plane 32-32 shown in FIG.31;

FIG. 33 is a sectional schematic view of a stent embedded within a bloodvessel and having been retrofitted with a sensor assembly according tothe invention;

FIG. 34 is a sectional view taken through the plane 34-34 shown in FIG.33;

FIG. 35 is a sectional schematic view of a stent embedded within a bloodvessel and showing a retrofit thereof with two sensor assembliesaccording to the invention;

FIG. 36 is a sectional view taken through plane 36-36 shown in FIG. 35.

FIG. 37 is a schematic representation of another embodiment of thesystem of the invention;

FIGS. 38A-38B combine as labeled thereon to illustrate an initial stentimplantation procedure;

FIGS. 39A-39H combine as labeled thereon to provide a flowchartillustrating the procedure and control carried out within the systemrepresented in FIG. 37;

FIG. 40 is an electrical schematic diagram of another sensor accordingto the invention employing a passive resonant circuit with temperatureresponsive capacitance;

FIG. 41 is a graph plotting capacitance variation with a desiredtemperature range; and

FIG. 42 is a graph schematically showing the graph of FIG. 40 incombination with an inductor core component exhibiting substantiallyuniform relative permeability over a temperature range of interest.

DETAILED DESCRIPTION OF THE INVENTION

While a variety of techniques for evolving an effective interstitialthermotherapy of target tissue volumes have been approached byinvestigators, an earlier development deemed somewhat promising involvedthe implantation of ferromagnetic alloy heaters sometimes referred to as“ferromagnetic seeds” within that volume. The ferromagnetic alloyheaters were adapted so as to alter in exhibited magnetic permeabilityin consequence of temperature. For example, with this arrangement, whena Curie temperature transition range was thermally reached, permeabilitywould, in turn, diminish over the transition range and correspondinglythermal responsiveness to an applied inductive field would diminish.Thus it was opined that a temperature auto-regulation could be achievedto optimize a thermally based implantation therapy. Such an arrangementis depicted in FIG. 1. Here, the treatment modality is representedgenerally at 10 wherein a target tissue volume, for example, comprisedof neoplastic tissue, is shown symbolically within dashed region 12located internally within the body of patient 14. Within the targettissue volume 12 a ferromagnetic material (e.g., ferromagnetic alloycomprising primarily palladium and cobalt) auto-regulating heaterimplant 16 is embedded which is, for instance, inductively heated fromthe excited inductive coil 18 of an alternating current field (ACF)heating assembly 20. The ferromagnetic implants as at 16 exhibit atemperature-related relative magnetic permeability, μ_(r). Such relativepermeability may be represented by curve 22 shown in FIG. 2. Relativepermeability is expressed as μ_(r)=μ/μ_(o), where μ=absolutepermeability (Henry/meter), μ_(o)=a constant=magnetic permeability offree space (Henry/meter) and μ_(r) is therefore dimensionless but rangesfrom a value of unity to 100,000 or more. Curve 22 reveals that therelative magnetic permeability, μ_(r), decreases as the temperature ofthe ferromagnetic alloy heater approaches its Curie temperature, T_(c).Since the induced electric field heating power in an object isproportional to the square root of magnetic permeability, a decrease inmagnetic permeability with elevation of temperature is associated with acorresponding decrease in the heating power associated with inductiveheating.

Traditionally, the change in magnetic permeability of ferromagneticalloys with increasing temperature has not been abrupt as would bepreferred for precise temperature regulation of an implanted heatingcomponent as at 16. In this regard, characteristic curve 22 reveals thatunder the relatively intense, applied fields a permeability transitionoccurs gradually over a span typically of 10° C. to 15° C. or more.Responses of ferromagnetic-based auto-regulators as represented at curve22 are occasioned both by the formulation of the ferromagnetic materialas well as its reaction to the imposed inductive field which is somewhatunavoidable for auto-regulation. As a result, the implanted heaterdevice 16 may not reach the intended Curie temperature and resultantrelative permeability of unity. Often, that elevation in temperatureabove normal body temperature has not been achieved. Accordingly,accommodation has been made by electing Curie temperature transitionranges falling well above what would have otherwise been a targettemperature for thermotherapy with a result that critical temperaturelimits of the tissue being treated have been exceeded. Because of suchperformance, thermotherapy utilizing such auto-regulating heatingimplants has been constrained to developing higher temperaturesincluding those deriving necrosis or cell death. Thermotherapeuticprocedures also are prone to inaccuracies by virtue of the unknownenvironmental conditions within which an implant as at 16 is situated.With respect to such unknown phenomena, temperatures achieved withferromagnetic implants will vary depending upon cooling phenomena withinthe tissue surrounding the device. Such phenomena occur, for example, asa consequence of the degree of vascularity in the target region andproximity of the heating element as at 16 to blood vessels. Thesevessels will tend to perform as inherent cooling mechanisms.Accordingly, while attempting to achieve an effective heat therapy, theauto-regulating implants as at 16 generally have been unable toestablish a necessary precise temperature output for requisitetherapeutic time intervals.

Now turning to the subject of the physiological consequence of elevatingtissue temperature, studies have been carried out to investigate boththe component of temperature elevation as well as the time componentwithin which such asserted higher temperatures are maintained, i.e., thetemporal aspect thereof.

-   -   (30) See: Niemz, M. H., “Laser-Tissue Interactions: Fundamentals        and Applications”, 2^(nd) Edition, Springer, Berlin,        GE (2002) p. 78.

Such investigations have established critical temperature and timerelationships which identify the occurrence of irreversible tissuedamage effects. In this regard, looking to FIG. 3, a generalizedsemi-log curve 24 is presented illustrating the temporal relationshipbetween the duration of the application of a given temperature to tissuewith the value of that critical temperature at which irreversible tissuedamage may occur. The system and method of the present invention areconcerned, inter alia, with maintaining the treatment of target tissuevolumes at accurately controlled temperatures for all heat-basedtherapies including hyperthermia. Hyperthermia is a form ofthermotherapy where there is an artificial elevation of the temperatureof a group of cells, a tissue, cell culture, or a whole organism forexperimental or therapeutic purposes. Heating of tissue throughthermotherapy techniques can induce a variety of biologic responses,depending on the intensity of the stress induced. When a tissue isheated, certain cells near the focus of the induced heating mayexperience greater heat shock than cells at a distance from the focus.Therefore, within a tissue being heated, a range of responses may occurat the cellular level. These responses of tissues to hyperthermia can bebroadly categorized. If the heat shock is too mild, there will be nodetectable biologic changes (over the basal level of “heat shock” geneexpression typical in the absence of heat shock). A mild heat shock mayinduce reversible cellular changes, including, for example, reversibledenaturation of proteins, triggering of ion fluxes from various cellularcompartments, activation of existing enzymes, and importantly, inductionof alterations in gene expression.

A more severe heat shock may irreversibly damage cellular components.Under certain conditions, when a cell is damaged, an ordered process,apoptosis, is induced that leads to the death of the damaged cell.Apoptosis is considered a form of “programmed cell death,” and cellsundergoing apoptosis often exhibit distinctive morphologic changes.Apoptosis is also involved in many developmental processes, defensiveresponses to microbial infection, the homeostasis of cell populations(e.g. lymphocytes) and as means of eliminating genetically damagedcells, such as cancer cells.

It is generally accepted that apoptosis is an active, highly organized,form of cell death, requiring both RNA and protein synthesis. A classicexample is the systematic death of a finite number of cells, 131, at acertain stage in the life cycle of the nematode Caenorhabditis elegans,a process controlled by the negative and positive regulation of specificgenes. As demonstrated by development in C. elegans, certain genes areinvolved in the regulation of cell death by apoptosis. A specificexample is the human gene bcl-2. In certain human follicular B-celllymphomas, deregulation of the expression of bcl-2 has been identifiedas a cause of the prolonged survival of the lymphoma cells. Alteredexpression of bcl-2 interferes with the typical programmed cell deathpattern, blocking apoptosis even when hematopoeitic growth factors areabsent.

Apoptotic cells exhibit a pronounced decrease in cellular volume,modification of the cytoskeleton that results in convolution of thecell, and eventual blebbing of the cell's membrane, compaction ofchromatin and its segregation within the nucleus of the cell. The DNA isdegraded into small fragments, and the apoptotic cell sheds smallmembrane-bound apoptotic bodies which may contain intact organelles. Theapoptotic bodies are phagocytosed (e.g. by macrophages) and the contentsof apoptotic bodies are intracellularly degraded, with little release ofthe contents of the apoptotic cells. In this manner, apoptosis does notinduce a localized inflammatory response.

Apoptosis is differentiated from necrosis by the general absence ofinflammation. It is a physiological type of cell death, part of ahomeostatic mechanism to maintain an optimal number and arrangement ofcells. In certain physiological conditions, massive apoptosis is notfollowed by necrosis and inflammation, such as the removal ofinterdigital webs during early human development, the regression ofliver hyperplasia following withdrawal of a primary mitogen and cellularloss in the premenstrual endometrium.

Where thermotherapy is sufficiently severe, cells and tissues are sodamaged that cellular integrity is destroyed, or the cellular machineryis so disabled that the induction of apoptosis does not occur. Incontrast to apoptosis, necrosis is a type of cell death morphologicallycharacterized by extensive cell loss, which results in the recruitmentof inflammatory cells. In necrosis, injured cells may exhibit clumpingof chromatin, swelling of the cell and organelles (demonstrating a lossof control of ion balance), flocculent mitochondria, and eventualbursting and disintegration of the necrotic cell. If necrosis isextensive enough, the architecture of a tissue is destroyed. Extensivenecrosis is characteristic of tissue destruction induced followingsevere damage by toxic chemicals, invasive microorganisms or ischemia.The wholesale release of cellular components into a tissue itself cantrigger a damaging inflammatory response.

When a tissue is damaged, cells may die by a combination of apoptosisand necrosis. Many agents capable of inducing necrosis also induceapoptosis. Apoptosis often precedes extensive necrosis, with apoptosisin these situations possibly acting in a self-protective manner. Whenthe level of insult to a tissue is too great, necrotic cell death cannotbe avoided. Murine mastocytoma cells have been reported to undergoapoptosis after a moderately severe heat shock, but the same cells dievia necrosis when the heat shock exposure is more severe.

For a comparison of apoptosis and necrosis, see:

-   -   (31) Columbano, A., “Cell Death: Current Difficulties in        Discriminating Apoptosis from Necrosis in Context of        Pathological Processes in vivo.” Journal of Cellular        Biochemistry, 58: 181-190 (1995).

The cellular response to a heat shock has been extensively studied.Certain heat shock inducible proteins such as Heat Shock Protein 70(HSP70), HSP 90 and gp96 are expressed constitutively at low levels.During mild to moderate heat shock, cellular proteins may undergoconformational changes. It is this alteration in the structure ofproteins, or other reversible denaturation effects, which are believedto play a role in inducing the heat shock response. (Note that otherstressors, such as nutrient deprivation, release of oxygen radicals, orviral infection may also induce conformational aberrations.) Following aheat shock, mRNA expression of the genes encoding HSP70, HSP 90 andgp96, for example (along with that of other heatshock responsive genes)is induced by activating proteins called “Heat Shock Factors.” Theresponse of two “Heat Shock Factors”, HSF-I and HSF-II is triggered bydifferent levels of thermal stress. As an example, HSP70 is thought tobe induced more rapidly than (by either less heat stress, or a shorterduration) HSP90. Therefore, different thermotherapy regimes will inducedifferent panels of heat inducible genes.

For additional background on the heat shock response see:

-   -   (32) Georgopoulos, C., Welch, W. J. “Role of the Major Heat        Shock Proteins as Molecular Chaperones.” Annu. Rev. of Cell        Biol., 9: 601-634 (1993).    -   (33) Hendrick, J. P. and Hartl, F. U., “Molecular Chaperone        Functions of Heat-Shock Proteins.” Annu. Rev. of Biochem., 62:        349-84 (1993).    -   (34) Lindquist, S., “The Heat Shock Response.” Annu. Rev.        Biochem., 55: 1151-91 (1986).    -   (35) Matzinger, “Tolerance and Danger: the Sensitivity of the        Immune System.” Annu. Rev. Immunol., 12: 991-1044 (1994).    -   (36) Morimoto R. I., “Perspective: Cells in Stress:        Transcriptional Activation of Heat Shock Genes.” Science 259:        1409-10 (1993).    -   (37) Morimoto, R. I., et al., “The transcriptional regulation of        heat shock genes: A plethora of heat shock factors and        regulatory conditions.” in Stress Inducible Responses, ed. by        Feige et al., Springer Verlag, Boston pp. 120, 139-163 (1996).    -   (38) Parsell, D. A. & Lindquist, S., “The Function of Heat-Shock        Proteins in Stress Tolerance: Degradation and Reactivation of        Damaged Proteins.” Annu. Rev. of Genet., 27: 437-496 (1993).    -   (39) Schlesinger, M. J., “Minireview: Heat Shock Proteins.”        Journal of Biological Chemistry 265: 12111-12114 (1990).

Initiation of a heatshock will induce conformational changes in cellularproteins, and lead to the induction of heat shock genes. HSP70 has theability to bind to proteins, is thought to act as a molecular chaperone,and may use an ATP dependant activity to renature stress-damagedproteins. It is thought that HSP 70 is involved in a process that‘repairs’ partially denatured proteins. If the native conformation of aprotein is not restored, then the denatured protein is degraded. Duringthe degradation process, HSP70 can retain a peptide fragment derivedfrom the degraded protein. In essence HSP 70 may then chaperone anantigenic peptide fragment of the denatured protein. These HSP70chaperoned fragments are then processed though the cell's endoplasmicreticulum and Golgi apparatus, and can then appear on the cell surface,presented by MHC-I molecules. Antigens presented on the surface of acell can then lead to an immune response being generated to thoseantigens.

In order to have processing of peptide fragments, and presentment ofpotentially immunogenic fragments on the cell surface, it is necessaryto have a living cell. An apoptotic cell, since the cellular contentsare degraded (for instance, without presenting antigens on thephagocytitic cell's surface MHC-I molecules), may have lowerimmunogenicity than either a heat shocked, but recovering cell or anecrotic cell.

Accordingly, with accurate temperature and time controls therapyemploying heat shock protein induction becomes available. Other adjuncttherapies available with accurately controlled thermotherapy are, forexample, release agent systems associated with a heating instigatedrelease, radiation treatment, chemotherapy and radiochemotherapy.

Some approaches utilized by investigators, in the use of hyperthermiatherapy, have achieved accurate temperature measurement and consequentcontrol by inserting temperature sensors such as fiber optic temperaturesensors, thermocouples or thermistors into the tissue adjacent to orintegrally with implanted heaters. These fiberoptic, thermocouple orthermistor-based sensors necessarily are tethered having one or moreelectrical or optical leads extending externally or to a surface regionof the body each time a hyperthermia therapy is administered. In thelatter regard, the somewhat involved procedure often must also berepeated a number of times over many weeks or months to effect thedesired therapeutic results. This becomes particularly problematic wherethe approach is employed in thermal therapy procedures associated withthe human brain. See generally:

-   -   (40) Hynynen, et al., “Hyperthermia in Cancer Treatment.”        Investigative Radiology, 25: 824-834 (1990).

Referring to FIG. 4, the noted tethered approach to sensing internaltarget tissue volume subjected to thermal therapy is illustratedschematically. In the figure, a targeted internal tissue volume 26 ofpatient 28 is shown to be under thermotherapy treatment. Thermal energyis applied to the target tissue volume 26 from the heating coil orantenna 30 of an ACF (alternating current field) heating assemblyemploying a heating modality as represented at block 32. The proceduretypically is carried out with a system structuring and control whichevokes the sought after heating and thermal distribution at the targettissue volume 26. One or more temperature sensors 34 a-34 d areimplanted strategically within the target tissue volume 26. Devices 34a-34 d are “tethered” in that electrical leads 34 a-34 d extendtherefrom through or adjacent to the skin to a temperaturemonitor/controller 38. Controller 38 additionally controls the output ofthe heating assembly 32 as is represented by arrow 40. In general, theheating carried out by the heating unit 32 may be enhanced through theutilization of heating elements implanted within the zone of the targettissue volume 26. A principal limitation of the technique illustrated inconnection with FIG. 4 resides in the requirement that the temperaturesensors 34 a-34 d must be inserted into and accurately positioned withinthe patient 28 each time thermotherapy is carried out and the proceduremay be repeated often; calling for a succession of accurate sensorpositionings. As noted earlier, the somewhat arduous insertion of theheat sensing elements 34 a-34 e becomes particularly intrusivelyundesirable where the procedure is carried out in conjunction with braintumor.

Should those sensors as at 34 a-34 d not be utilized, the temperaturesreached at the target tissue volume 26 during a procedure can only beapproximated by modeling methods which are subject to substantial errordue to physical differences in the tissue of given patients. In thisregard, tissues will exhibit differences in vascularity, as well asotherwise assumed average properties. As noted hereinbefore, vascularityfunctions as a conveyance for heat removal in the vicinity of thetargeted tissue region. For further discussion of thermal modeling basedmethods of thermotherapy, reference is made to publication (10) supra.

The present invention employs temperature sensing untethered implantswhich are located within a target tissue volume, whereupon, using any ofthe above-discussed extra body heating systems the untethered implantswill provide a quite accurate readout of preselected temperature levels.These temperature sensing implants are configured as passive resonantcircuits with an inductor component and a capacitor component configuredas a resonant circuit. That circuit is caused to ring at a known uniqueresonant center frequency while the tissue being monitored is at monitortemperatures below a target Curie temperature. When the predeterminedsetpoint (Curie-based) temperature for the tissue is reached, then theknown resonating center frequency abruptly terminates. This sharptermination of resonance in conjunction with the known center frequencyis achieved by utilizing an inductor component comprised of a windingand a ferromagnetic core. The ferromagnetic core is formulated to evokea Curie transition, for example, in magnetic permeability overrelatively narrow temperature ranges, for instance, between about 0.1°C. to about 5° C. for use with sensors and as narrow as about 0.1° C. toabout 1° C. for use with auto-regulating heaters. This transition interms of relative magnetic permeability μ_(r), will be from about 100 to1 to about 5000 to 1.

A highly advantageous aspect of this inductor component when employedwith a passive resonant sensor resides in a stabile maintenance of theresonant center frequency of the sensors during the transitionapproaching the Curie temperature setpoint. During the transition, whilethe intensity amplitude of the sensor output diminishes, its selectresonant center frequency persists. As a consequence, a targettemperature predictive form of control is made available. In general,control is based upon a predetermined ratio of the instantaneous valueof a signal representing the amplitude of the detector signal at theunique resonant center frequency to the maximum detector amplitudewitnessed.

Returning to FIG. 2, a representation of the permeability/temperaturecharacteristic of the inductor component ferrite of the passive resonantsensors is shown at dashed line 40 having a knee at 42 and a Curietransition range at arrow pair 44. As the relative permeability passesthe knee 42 sensor output at its unique resonant center frequency willcommence to diminish with respect to the amplitude of its intensity.Preferably the Curie transition range will be from about 1° C. to about2° C., but may be within a range of about 0.5° C. to about 5° C. Shouldthe Curie temperature be, in fact, reached the resonant center frequencywill shift upwardly, in effect, to an off-scale value. However, systemcontrol preferably is carried out before that temperature is reached.

Where autoregulating heater implants are employed with the sensors ofthe invention, then the above-noted narrow Curie transistor range as itis present without inductive influence is desirable. Such a narrow rangeis represented in FIG. 2 at dashed curve as having a knee 48 commencingthe Curie transition. The narrow transition range is represented atarrow pair 50. Because the sensors are of such small size, themethodology of the invention can be employed in connection with magneticresonant imaging (MRI) without adverse consequence.

The temperature sensing implants may be designed to perform at theirpredetermined resonant center frequencies as the targeted tissue heatsto a lower threshold setpoint or target level. As that Curietemperature-based threshold setpoint is approached within a Curietransition range, the output intensity of the involved sensor at itsunique resonant center frequency diminishes. When the threshold Curietemperature setpoint is reached, the resonant center frequency, ineffect, shifts to an off-scale value. These lower threshold temperaturemonitoring sensors may be combined with temperature sensing implantswhich experience the sharp Curie transition at an upper limit of tissuetemperature. Accordingly, as the Curie temperature-based limit setpointis approached within a Curie transition range, the output intensity ofthe involved sensor at its unique resonant center frequency diminishes.When the limit Curie temperature is reached, the resonant centerfrequency, in effect, shifts to an off-scale value. Thus, in effect, thedesired thermotherapy temperature range is bracketed.

The passive resonant sensors with inductors exhibiting the Curietransition characteristic may be employed as threshold temperaturemeasuring implants in conjunction with auto-regulating heatersexhibiting Curie temperatures above the sensor threshold temperaturelevels. Because such heaters require an inductive heating modality theirCurie temperature based transitions ranges will be affected. Howeverwith the noted ferromagnetic materials the Curie temperature transitionswill be within much narrower temperature ranges than heretofore havebeen observed. Looking to FIG. 5, a curve or curves relating relativemagnetic permeability, μ_(r), with temperature again are revealed. Inthe figure, curve 52 shows the performance of this ferromagneticmaterial under the influence of low level applied magnetic fieldintensities. Note the sharp transition approaching Curie temperatureT_(C). Where necessary high level applied magnetic field intensities areutilized with the auto-regulators, an adequate but not as sharp Curietransition occurs as represented at curve 54. In general, in order toavoid interference of the high level applied magnetic field with thetemperature monitoring passive temperature sensors the inductive fieldsare applied intermittently with the interrogation-based monitoring ofthe temperature sensors. This assures the sharp Curie transitionperformance with the temperature sensing implants. Depending upon theconditions involved with a particular thermotherapy procedure, theauto-regulator implants also may be employed with both lower thresholdtemperature determining sensor implants and upper limit temperaturesensing implants. Nonmagnetic metal heating sheaths also may be combinedwith the ferrite cores of the temperature sensors themselves. However,this is not a preferred arrangement inasmuch as the sensor associatedwith a heater sheath will tend to measure the temperature of the heatersheath as opposed to the tissue within which the temperature sensor isembedded. Separate heating components are useful where a more controlledlocalization of target tissue volume heating is called for.

Now turning to the soft ferromagnetic materials employed with theinductor components of the passive resonant circuit based temperaturesensing implants as well as the auto-regulating heaters, ferrites havebeen considered to be crystalline reaction products of the oxides ofiron and one or more other bivalent metals or bivalent metalliccomplexes. The soft magnetic materials are generally categorized asexhibiting a high inductance, B, for a low field, H.

Particularly for the predominating hyperthermia based proceduresdescribed herein, the soft ferrites are formulated to derive relativelylow Curie point values within, for instance, a range extending fromabout 39° C. to about 65° C. and more typically within a range extendingfrom about 41° C. to about 50° C. Generically, ferromagnetic materialsexhibit pronounced magnetic effects occurring in atoms and ions and stemfrom only a limited number of metallic elements, to wit: Fe, Co, Ni andcertain rare earths. Alloys or oxides of these materials typically willcontain neighboring ions such as Mn to substantially enhance the atomicspin effect. Zn substitution both increases the magnetic moment of Mnand Ni ferrites and lowers the Curie temperature point of a resultantproduct. Such substitution will be seen to appear in ferriteformulations disclosed herein. The metal ion present in largestconcentration in ferrites is Fe³⁺. Because of its high ionic moment ithas a high potential for controlling magnetic characteristics. Sucheffects are not chemical but crystallographic, being related to latticesite distribution.

The processes for preparing ferrites have an extensive but relativelyshort history. Such processes generally reflect the common goal offormation of a spinel structure. Starting materials typically are oxidesor precursors of oxides of the cations and their processing involves aninterdiffusion of metal ions of a select composition to form a mixedcrystal. Ferrite powders have been produced by precipitation anddigestion methods. These powders are blended, calcined and milled and,for the case of spinel ferrites, sintered for a variety of purposesincluding: (a) completing the interdiffusion of the component metal ionsinto a desired crystal lattice; (b) establishing appropriate valencesfor the multi-valent ions by proper oxygen control; and (c) developing adesired microstructure. During this procedure, the materials areconsolidated into a body or component, for example, by die-pressing.

Referring to FIG. 6, a flow chart is presented describing the mostcommonly utilized ceramic process for forming manganese zinc ferrites.As represented at block 60, oxides of the metals are first blended in aratio according to the desired composition, here providing for a desiredCurie point characteristic. The oxides are milled, and as represented atarrow 62 and block 64, the resulting oxide mixture is subjected to athermal treatment called calcining wherein ferrite material issynthesized by a solid state reaction. Generally, this step is performedin air and only a partial ferrite formation is accomplished. Next, asrepresented at arrow 66 and block 68 the calcined material thus obtainedis then milled in order to reduce its particle size and homogenize thematerial. This step is commonly performed in a steel ball mill. Asrepresented at arrow 70 and block 72 an organic binder is usually addedat this stage in order to control subsequent steps of granulating orspray drying and pressing. Next, as represented at arrow 74 and block76, in the preliminary stage of the sintering process, the pressedferrite part is subjected to an oxidizing treatment. The aim of thistreatment is to remove the organic binder added previously which at thisstage is burned off by heating the ferrite part in air. Next, asrepresented at arrow 78 and block 80, at a later stage of the sinteringprocess a “soak” is introduced with the aim to restore the oxygenstoichiometry wherein the ferrite part is kept at a high temperature inan atmosphere deficient in oxygen with respect to that of thestoichiometry ferrite.

One ferrite exhibiting a sharp Curie point transition of 44.5° C.exhibited the following chemistry:

-   -   Iron 49 wt %    -   Zinc 15 wt %    -   Manganese 9 wt %    -   Oxygen 27 wt %

In addition, calcium oxide may be added to the above formulation toadvantageously increase the electrical resistivity of the ferritematerial to greater than 100 ohm-cm, preferably greater than 500 ohm-cmand more preferably greater than 700 ohm-cm. This serves to increase theamplitude of the signal generated by the resonant circuit of the sensor.

See generally the following publications:

-   -   (41) Yoshifumi, A., et al., “Preparation and Evaluation of        Temperature Sensitive Magnetic Thin Film With Low Curie        Temperature”, T IEEE Japan, 118-A(2): 158-163 (1998).    -   (42) Goldman, “Handbook Of Modern Ferromagnetic Materials”,        Kluwer Academic Publishers, Norwell, Mass. (1999).

Referring to FIG. 7, a schematic representation of the resonant circuitprovided with each temperature sensing passive implant is representedgenerally at 90. Circuit 90 is configured with a ferrite core component92 having a Curie transition range extending to the target or setpointtemperature. Turns 94 of an inductive winding are shown wound about thecore 92 to provide an inductive component. Start and end termini of thewindings 94 are seen to extend at leads 96 and 98 to a series couplingwith a capacitor 100. The inductance which may be designed for implant90 may be represented by the following expression:L=(const.)μ_(r) AN ² /l

-   -   Where L is inductance; μ_(r) is relative permeability;    -   A is the cross-sectional area of the core 92;    -   N is the number of turns of the winding 94; and    -   l is the length of the ferrite core component 92.        As is apparent, the value of inductance may be developed by        adjusting the number of turns, N. When excited by an excitation        electromagnetic field from an extra body location, the circuit        90 will resonate in accordance with the expression:

$f_{0} = \frac{1}{2\pi\sqrt{LC}}$

-   -   where f₀=the resonant center frequency of the resonant circuit;    -   L is inductance; and    -   C is capacitance.

With this arrangement, a plurality of temperature sensing implants maybe developed, each with a unique resonant center frequency. Theparticular resonant frequency which is utilized in carrying outtemperature sensing of a target tissue volume in general, will fallwithin a range of from about 100 kHz to about 2 MHz. As is apparent fromthe above two expressions, when the circuit 90 is exposed totemperatures approaching the Curie temperature, relative permeabilitywill drop to a value approaching one and, in consequence, the reluctanceof the inductor cast decreases and the associated signal output levelissuing from the sensor decreases by 3-fold to 10-fold or more,indicating that the Curie temperature is close at hand. The aboveexpressions also reveal that the various resonant frequencies employedwith the system can be adjusted by controlling the number of turns 94and the value of capacitance for capacitors as at 100. Accordingly, eachtemperature sensor implant will exhibit its own unique resonant centerfrequency based signature.

In general, the windings 94 are formed of materials including copper,silver, gold, aluminum, platinum or other non-magnetic, low electricalresistivity metals or alloys and will exhibit diameters within a rangeof from about 0.001 inch to about 0.020 inch and preferably from about0.002 inch to about 0.010 inch; and most preferably within a range ofabout 0.003 inch to about 0.007 inch. Because the temperature sensingimplant circuits as at 90 are excited from an extra body appliedexcitation electromagnetic field generated as a broad spectrum pulseexhibiting an excitation interval, it is desirable that resonant ringingof circuits as at 90 continue for an interval extending beyond thatexcitation interval. To achieve this ringing persistence interval it hasbeen found desirable to configure the implant circuits as exhibiting ahigh quality factor, Q. Q is a measure of the sharpness of a resonantpeak at the −3 dB point. The Q of a series RLC circuit may be expressedas follows: Q=˜₀L/R. Accordingly, it is desirable to maintain lowervalues of resistance which is a factor in the selection of a particularinductive winding wire diameter. It is preferred that the inductivewindings 94 be in a single layer in order to avoid a resistanceelevating proximity effect. However, in general, between one and aboutten layers may be employed. The dimensions for the core length, l, canvary substantially, for example, within a range of from about 5 mm toabout 100 mm; more preferably from about 5 mm to about 40 mm; and mostpreferably, from about 5 mm to about 20 mm.

Referring to FIG. 8, a schematic and block diagrammatic illustration ofthe system at hand is presented. Represented generally at 110, thesystem is shown to include an excitation antenna 112 located in a plane114 which, in general, will be located beneath the patient. A passiveresonant sensor implant will have been located within the target tissuevolume of the patient. An exemplary temperature sensing implant isrepresented at 116. Extending over and about the implant 116 is a sensorantenna 118, having a diameter of about 18 inches. Excitation antenna112, may, for example, be provided as a single turn of 14 awg wirehaving a diameter of about 20 inches. Antenna 112 is seen coupled viacable 120 to the output of an excitation assembly represented at block122. Assembly 122 functions to supply an excitation pulse of about onemicrosecond duration from a 1000 volt power supply. Accordingly, theexcitation antenna 112 may carry a 40 amp peak current with a waveshapethat is approximately one cycle of a damped sinusoid. In this regard,note that the high voltage power supply is represented at block 124having a plus output line 126 extending to antenna 112 and a negativeoutput line at 128. A high voltage storage capacitor function, C1 islocated between lines 124 and 128 as represented at line 130. Alsorepresented at line 130 is a small sense resistor function, R1. Line 130also is shown extending to a gate drive transformer 132 which receives agating input at node, A, and functions to gate a high voltage transistorfunction Q1 into conduction. Note that one side of transistor Q1 iscoupled with line 130, while the opposite side, represented at line 133,extends with steering diode D1 to a line 134 coupled to antenna 112.Line 134 additionally extends with steering diode D2 to line 130.

A gate drive circuitry is represented at block 136 shown connected toline 132 via line 138 and providing the earlier-noted gating pulse, A.Gate drive circuitry 136 is actuated in response to a forward driveinput represented at arrow 140. That input is derived at a fiberopticinterface circuit represented at block 142 which is seen responsive toan optical drive input represented at dashed arrow 144. An interfaceoptical output is represented at dashed arrow 146. In operation, when aforward drive gating pulse is applied to transistor Q1 for about onemicrosecond current flows from the storage capacitor function C1 throughexcitation antenna 112, then returns through diode D1, transistorfunction Q1 and returns to the storage capacitor function C1. Thatrepresents the forward half-cycle of excitation of antenna 112. Whentransistor Q1 is turned off, current flows through diode D2, throughexcitation antenna 112 and returns to the capacitor function C1. Theresult is a single cycle sinewave excitation. Sense antenna 118 isblocked during this excitation interval, inasmuch as the excitationfield generated from excitation antenna 112 will tend to couple withantenna 118. Antenna 118, which may be provided as a paired wire deviceis connected through cable 148 to a detector and control functionrepresented at block 150. Function 150 includes fiberoptic interfacecircuitry represented at block 152. Circuitry 152 is seen to beinteractively associated with optical transmission arrows 144 and 146and is powered as represented at arrow 154 from a low voltage linearpower supply represented at block 156. Power supply 156 additionallypowers a timing and control logic function shown at block 158 asrepresented at arrow 160. Function 158 serves to carry out appropriatelogic including the duration of the excitation pulse, delays before theenablement of antenna 118 and the like.

Also powered from low voltage linear power supply 156 as represented atarrows 162 and 164 is a front-end amplification function represented at166 and an output amplification function represented at 168. Thedetected signals from sense antenna 118 are both amplified and filteredfollowing a delay interval occurring subsequent to the excitationinterval. That delay interval permits a sufficient dampening of theexcitation pulse so as not to interfere with the resonating signalsemanating from the sensor implant or implants. Note that cable 148extends to the input of a front-end amplification stage 166. The outputof the detector assembly also is seen to be amplified as represented atsymbol 168. As part of the signal treatment, as represented at arrows170 and 172, the sense antenna output is subjected to bandpass filteringas represented at block 174 as well as is stripped of any d.c. term. Thebandpass evoked by the filtering function 174 will extend from, forexample, about 100 kHz to about 2 MHz.

The amplified sense output is directed, as represented at arrow 176 to adata acquisition and control network represented in general at block178. This analog signal is sampled at a very high rate with an analog todigital conversion approach. With this digital approach, the system mayapply the full power of signal averaging to lower baseline noise withrespect to the associated function of identifying thermal sensorbroadcast centerline frequency data. For example, utilizing apoint-by-point approach averaging is carried out and resonant frequencydata is derived. For that purpose, Fourier transform approaches areavailable including the fast Fourier transform (FFT). These functionsare represented at block 178 as a data acquisition block 180, thedigital output of which is represented at arrow 182. Arrow 182 extendsto a data processing algorithmic function represented at block 184. Thisalgorithm is responsive to the center frequency intensity signal anddata representing a corresponding unique resonant electromagneticresponse of an implant temperature sensor to derive implant status dataas detector outputs. These Fourier-type outputs representing a uniqueresonant center frequency will diminish in amplitude as core Curietemperature is approached. A ratio of such diminution (instantaneous tomaximum amplitude) is used for control and monitoring purposes. Asrepresented at bus arrow 186 and block 188 resultant implant status datais asserted to a graphical user interface or readout assembly to providevisibly discernable information to the operator. Signals to instruct thesystem to commence carrying out an excitation and sensing sequence maybe evolved from the data acquisition function 180. Such signalintroduction is represented at arrow 190.

Referring to FIG. 9, oscillotraces are presented which were derived froma bench testing of the temperature sensor implants. Five of the sensorimplants were utilized having a 1.5 mm diameter and a length of 20 mm.The sensors were configured to derive outputs with center resonantfrequencies of 400 kHz, 500 kHz, 700 kHz, 800 kHz and 900 kHz. Curietransition temperatures for all but the 500 kHz device were 41° C., the500 kHz device having a Curie temperatures of 44° C. These five sensorswere located in an array pattern on an approximately 1 cm grid. Thisgrid was located within a water bath having a temperature of 25° C. Thebottom of this water bath was located at the plane of an excitationantenna having a diameter of 20 inches and formed of the earlier-noted14 awg wire. The sense antenna was arranged having a diameter of 18inches and was formed of paired turns of 20 awg wire and located 12inches above the excitation antenna. In the figure, the trace at level198 is the current waveform that was used for triggering. However, thewaveform is not visible in the figure. The trace at level 200 is a timedomain representation of the analog amplified output of the senseantenna-based detector system. Level 202 represents a fast Fouriertransform (FFT) of level 200. The scale for level 202 is 500 kHz perdivision. The system also averaged eight acquisitions to derive theseFFTs at level 202. Frequency intensity identifier 204 is the FFTresponse from the 400 kHz sensor. Frequency intensity identifier 205 isthe FFT based response to the 500 kHz based sensor. Frequency intensityidentifier 206 is the FFT based output representation for the 700 kHzbased sensor; frequency intensity identifier 207 is the FFT derivedevaluation of the output of the 800 kHz sensor; and frequency intensityidentifier 208 is the FFT based evaluation of the output of the 900 kHzsensor. A spike at 210 is a spurious anomaly. It was determined thatmoving the array up or down on a Z-axis had an effect on amplitude ofthe FFT outputs but not on the frequency spacing. Likewise moving themin the X and Y directions within the cylinder-defined by the excitationand sense antennae had no effect upon frequency spacing. As the sensorarray was heated the pattern remained very stable until a temperature ofabout 41° C. was reached, whereupon identifiers 204 and 206-208disappeared, however, the identifier 205 remained. Following the aboveexpressions, as the Curie temperature of the sensors is reached,inductance dropped, for example, by a factor of 10. As that occurs, apeak extant, for example, at 400 kHz now becomes a peak at 4 MHz.

An initial concern in the earlier investigations of the instant systemwas addressed to the slight change in relative permeability which mayoccur when a given implant sensor was approaching or transitioningtoward its Curie temperature. The question was posed as to whether theresonant center frequency position would shift during the temperatureinterval of Curie transition so as to despoil the necessary FFT derivedcenter frequency spacing. As the sensors were heated toward their Curietemperatures, resonant center frequencies remained stable and did notincrease or shift. Looking to FIG. 10A a representation of the FFTamplitudes of four sensors 212-215 having differing resonant centerfrequencies (kHz) is provided. The figure illustrates typicallyencountered FFT relative amplitudes corresponding with the intensity ofthe resonant output of the sensors when at monitoring temperatures wellbelow Curie temperatures.

Now referring to FIG. 10B the FFT relative amplitudes of the same foursensors 212-215 are illustrated during the course of a Curie temperaturetransition. Note that the resonant center frequencies have remainedstable, but the detector output FFTs have diminished in relativeamplitude as the temperatures monitored by the sensors approached butdid not reach Curie temperature.

Referring to FIG. 10C, actual sensor performance in a bath of waterwhich was heated over a period of time is plotted with respect totemperatures and sensor output signal strength ratio for two sensors. Athermocouple was plotted with each sensor and the time/temperature plotsthereof are shown at curves 216 and 217. Curve 218 plots the signalstrength ratio of a sensor having a 41° C. Curie temperature. Note thatas associated temperature curve 216 rises from a nominal human bodytemperature of about 37° C. the signal strength ratio remains at one atregion 219, then commences to drop; essentially dropping into noise asthe bath temperature closely approached 41° C.

Curve 220 plots the signal strength ratio of a sensor having a 45° C.Curie temperature. Note that as its associated temperature curve 217elevates from a normal human body temperature of about 37° C., thesignal strength ratio remains at one at region 221, then commences todrop, essentially dropping into noise as the bath temperature closelyapproached 45° C.

The control system associated with this form of sensor performancemeasures the initial (FFT) signal amplitude for each sensor with respectto its unique resonant center frequency. Typically there resonant centerfrequencies are separated by about 50 kHz to about 75 kHz. The relativeamplitude of the Fourier transform based signal of each sensor istracked. When that relative amplitude (representing the ratio of theinstantaneous amplitude to its initial amplitude) diminishes or drops toa select value, the setpoint temperature is assumed to have beenreached. In this regard, the extent of any thermal overshoot is somewhatminimized.

Amplitude ratio ranges for this control approach may range from about0.2 to about 0.7 and preferably from about 0.3 to about 0.5. Thetemperature value at the commencement of the Curie transition range,i.e., at the knee 42 (FIG. 2) is very reproducible (to within about 0.5°C.) but is slightly lower than the true Curie temperature. A Curietransition range of about 0.1° C. to about 0.5° C. is decreased inconnection with FIG. 2. The preferred transition temperature will beabout 1° C. to about 2° C. lower than Curie temperature.

Referring to FIG. 11A, the high voltage power supply, switching, andassociated gate drive circuitry as described in connection with FIG. 8are illustrated in schematic fashion. In the figure, the high voltagepower supply described earlier at 124 is shown being provided as aswitching power supply 226 having a +12V input at line 228 and providinga positive output at line 230 and a negative output at line 232. Lookingmomentarily to FIG. 11B, the +12V input to device 226 is derived from anoff-board power supply (not shown). That input is imported via aconnector 234 with ground output at line 236 and +12V output at line238, a filtering capacitor C2 being connected between lines 236 and 238.Returning to FIG. 11A, device 226 may be provided, for example, as an“A” Series High Voltage Power Supply model 1A12-P4, marketed byUltravolt, Inc., of Ronkonkoma, N.Y. The output of device 226 at lines230 and 234 may be adjusted at a potentiometer 260. Inasmuch as thepower supply 226 is of a switching variety, it may be desirable toprovide its enablement, for example, only during an excitation intervalor portion thereof. Enablement is provided, for example, at lines 262and 264, by the assertion of a high voltage enable signal input, HV_EN.

A steering diode D3 is seen positioned within output line 230. Diode D3functions to block downstream voltages and thus protect device 226.Similarly, diode D4 coupled between output lines 230 and 232 within line266 protects device 226 against the application of a reversed voltage.Downstream of device 226 are three energy storage capacitors C5-C7corresponding with capacitor function C1. In this regard, capacitor C5is coupled between output lines 230 and 232 at line 270; capacitor C6 iscoupled between those output lines at line 271; and capacitor C6 iscoupled between the output lines at line 272. Line 232 extends to oneinput of a header 274 while opposite output line 230 extends to anopposite terminal of that device. Header 274 is connected withexcitation antenna 112 which is connectable with header 274 at lines 276and 278. A ballast resistor R3 is coupled within line 230 and functionsas an inrush current limiter with respect to capacitors C5-C7.Additionally, the high voltage across lines 230 and 232 is monitored atline 280 which is coupled intermediate resistors R4 and R5. Theseresistors correspond with sensor resistor function R1 described inconnection with FIG. 8.

Monitoring line 280 extends to a voltage monitoring network representedgenerally at 290. In this regard, line 280 extends to lines 292 and 294.Line 294, in turn, extends to the positive input of a comparator 296.Line 292 additionally incorporates a Schottky diode D5. Diode D5functions to protect the network 290 from overvoltages. The oppositeinput to comparator 296 is provided by a precision reference networkrepresented generally at 298 comprised of zener diode D6, capacitor C8and resistor R6. These components combine to provide a reference inputat line 300 of, for example, 2.5 volts. The output of comparator 296 atline 302 is of an open collector variety and therefore incorporates apull-up resistor R7 and noise protecting bypass capacitor C9. ResistorsR8 and R9 within line 280 function to provide comparator hysteresisperformance. When the high voltage across lines 230 and 232 is at anappropriate level, for example, 1000 volts, a logic high true signal,HV_OK is generated.

Looking to that circuitry, gate drive circuitry 136 (FIG. 8) again isrepresented in general by that identifying numeration. The excitationpulse to excitation antenna 112 is of about one microsecond duration andis generated in response to an excite or forward drive (FD) signalasserted at line 304 extending to the input terminal of a driver 306Line 304 is coupled to +5V through pull-up resistor R11 at line 308.Driver 306 is configured with resistor R12 and capacitors C10 and C11 toprovide an excite output at line 310. Inasmuch as the excite signal atline 310 drives an inductive device, a protective Schottky diode D7 isprovided between it and ground. Driver 306 may be provided, for example,as a 14 Amp Low-Side Ultrafast MOSFET Driver, type IXDD414PI, marketedby Ixys Corp., of Santa Clara Calif. Line 310 incorporates resistor R13and extends to the primary side of isolation transformer 132. Thesecondary side of isolation transformer 132 is coupled via line 312 tothe gate of power transistor Q1 and via lines 314 and 316 to itsemitter. The gate drive to transistor Q1 includes a steering diode D8,resistors R16 and R17 and transistor Q2 which functions to causetransistor Q1 to turn off quickly. A zener diode D9 protects the gatedrive from overvoltages, while diode D10 protects the drive transistorfrom reverse voltages.

Excitation transistor Q1 performs in conjunction with two steeringdiodes to apply excitation energy to excitation antenna 112 as describedin connection with FIG. 8. Those diodes as well as transistor Q1 areidentified with the same numeration as described in connection with thatfigure. In this regard, a collector of transistor Q1 is coupled via line318 incorporating steering diode D1 to 3×2 header 274 via line 314. Theemitter of the excitation transistor is coupled through steering diodeD2 and resistor R18 to header 274. Line 320 extending from header 274 toline 314 completes the excitation circuit. In general, transistor Q1 isturned on for about one microsecond to effect excitation of exciteantenna 112 for one half of a sinusoid. The transistor then is turnedoff to permit generation of the opposite half cycle.

Referring to FIG. 11C, a power supply 240 is seen coupled with +12V atline 242 to provide a +5V output at line 244. Lines 246 and 248 extendrespectively from the GND and OV terminals of device 240 to line 250incorporating filtering capacitor C3.

Referring to FIG. 11D, connector 252 having inputs at lines 254 and 256and configured with resistor R2 and capacitor C4 provides another +5Vinput.

An interrogation cycle for the system at hand involves an initialexcitation of excitation antenna 112 followed by a short, for example, 2microsecond delay, following which data is acquired from sense antenna118 (FIG. 8). For the instant demonstration, a START or START_FRAMEsignal is derived, for example, from a data acquisition and controlnetwork to commence each of these interrogation cycles. Looking to FIG.11E, the receiver component of a optoisolator as shown at 326 serves toreceive and transfer this START signal via line 328 to line 330. Device326 is configured with capacitor C14 and may be provided, for example,as a 40 kBd 600 nm Low Current/Extended Distance Link Receiver, type HFBR-2533 marketed by Agilent, Corp., of Palo Alto, Calif. Line 330 iscoupled through pull-up resistor R19 to +5V and extends to the input aninverter 332 to provide the START_FRAME signal at line 334.

Referring to FIG. 11F the START_FRAME signal reappears in conjunctionwith line 334 extending to an input of a programmable logic device (PLD)340. Representing a component of the control circuit of the system athand, PLD 340 is configured with filter capacitors C15-C18 and receivesa clock input at line 342 from the clock network represented generallyat 344. Network 344 is comprised of a 1 MHz crystal configured withcapacitors C19 and C20, resistors R20 and R21 and inverters 348 and 350.Inverter 348 is configured with capacitors C21 and clock input line 342incorporates an input resistor R22.

A start-up reset function is provided by a device 354, which isconfigured with resistor R23 and provides a Clear input signal to PLD340 via line 356. Device 354 may be provided as a Supply-VoltageSupervisor and Precision Voltage Detector, model TL7757CD marketed byTexas Instruments, Inc. of Dallas Tex. PLD 340 further is configuredwith resistors R26 and R27 and is programmable from junction device 358having outputs at lines 360-363, which are coupled with pull-upresistors R28-R34. PLD 340 receives status information, for example, theHV_OK signal at line 302, interlock information and the like and whereoperational criteria are in order, provides a STATUS_OK signal at itsoutput line 366. Additionally, the HV_OK signal is employed to providethe power supply enabling signal, HV_EN at line 368. That signal may bedirected to acquisition and control circuitry and additionally may beemployed to enable power supply 226 as described in connection with line262 in FIG. 11A. In the presence of the status signal line 366 and highvoltage enable signal at line 368, PLD 340 may respond to a START_FRAMEsignal at line 334 to derive the excite or forward drive signal, FD atline 370. It may be recalled that the excite signal is directed to line304 in FIG. 11A. Following an appropriate excitation delay permittingboth the development of the second half cycle of the excitation sinusoidand sufficient damping to permit activation of the detection system, anACQUIRE signal is generated at line 372.

The STATUS_OK signal from line 366 is optically transmitted to theacquisition and control features of the system. Looking to the FIG. 11Gthe STATUS_OK signal is seen introduced via line 380 to the input of anopto-transmitter represented generally at 382. Transmitter 382 may beprovided as a 1 MBd 600 nm High Performance Link Transmitter, modelHFDR-1532 marketed by Agilent, Corp. of Palo Alto, Calif. Line 380 iscoupled to +5V through pull-up resistor R35. Device 382 is configuredwith transistor Q3, light emitting diode D11 and resistors R36-R38.

In similar fashion the ACQUIRE signal at line 372 (FIG. 11F) isoptically transmitted both to detection circuitry and to control andacquisition circuitry of the system. Looking to FIG. 11H the ACQUIREsignal is asserted via line 384 to the input of an opto-transmitterrepresented generally at 386. Device 386 may be provided as a 40 kBd 600nm Low Current/Extended Distance Link Transmitter type HBR-1533 marketedby Agilent, Corp., of Palo Alto, Calif. The device is seen configuredwith transistor Q3, light emitting diode D12, resistors R39-R41 andcapacitor C22.

Device 382 optically conveys the STATUS_OK signal to an optical receiverfor further disposition. Referring to FIG. 12A the STATUS_OKopto-receiver is shown at 390. Device 390 is configured with capacitorC24 and resistor R44 and may be provided as a 40 kBd 600 nm LowCurrent/Extended Distance Link Receiver model HFBR-2533 marketed byAgilent, Corp. (supra). The output of receiver 390 is directed to a linedriver 394 which functions to provide a corresponding STATUS_OK outputat line 396 incorporating resistor R45. Looking momentarily to FIG. 12B,a connector 398 is shown receiving the STATUS_OK signal at line 400 forpurposes of conveying that signal to control and data acquisitionfunctions of the system. Returning to FIG. 12A, device 394 is seen to beconfigured with resistors R46 and R47 and capacitor C25.

The ACQUIRE signal generated from PLD 340 and transmitted viaopto-transmitter 386 is received at opto-receiver 402. Device 402 isconfigured with capacitor C26 and resistor R48 and may be provided as a1 MBd 600 nm High Performance Link Receiver, model HFbR-2532 marketed byAgilent Corp. (supra). The output of device 402 at line 404 is directedto an input of line driver 394 to provide a corresponding output at line406 incorporating resistor R49 and extending to a BNC connector 408.Connector 408 is employed to convey the ACQUIRE signal to control anddata acquisition functions of the system. Note, additionally, that thesame ACQUIRE signal is tapped from line 406 at line 410. Returningmomentarily to FIG. 12B, the ACQUIRE signal is seen to be asserted atline 412 to earlier-described connector 398. Note additionally in thatfigure, that the START OR START_FRAME signal is derived from the controlsystem as represented at line 414.

Returning to FIG. 12A the START_FRAME signal reappears as being assertedat line 416. Line 416 is seen coupled through pull-up resistor R50 to+5V and to ground through resistor R56. Line 416 also is coupled vialine 418 to an electrostatic discharge (ESD) and over-voltage protectivedevice 420. Note that the ACQUIRE and STATUS_OK signals also are coupledwith device 420 as seen at respective lines 422 and 424. Devices as at420 may be provided as an SCR/Diode Array for ESD and TransientOver-Voltage Protection, model SP724AH, marketed by Littelfuse, Inc., ofDes Plaines, Ill. Line 416 incorporates a resistor R51 and extends to aninput of driver 394. The corresponding output from driver 394 at line426 extends to the input of an optical transmitter represented generallyat 428. Device 428 is configured with a light emitting diode D14,transistor Q4 and resistors R52-R54 and may be provided as a 40 kBd 600nm Lower Current/Extended Distance Link Transmitter model HFBR-1533marketed by Agilent, Corp. (supra). Device 428 functions to opticallyconvey the START_FRAME signal to opto-receiver 326 described inconnection with FIG. 11E. Driver 394 further is configured withresistors R55-R59 which are coupled respectively to input terminalsA2-A7 and ground.

FIGS. 12F and 12D should be considered together in the manner labeledthereon. Referring to FIG. 12C, the linear power supply described inconnection with FIG. 8 at 156 is identified in general with that samenumeration. Power supply 156 receives line input at connector 440. Lines442 and 444 extending from the connector are operatively associated witha current limiting varistor 446. Lines 442 and 448 as well as line 450extend to one primary winding component of a step-down transformerrepresented generally at 452. Lines 448 and 450 are tapped by respectivelines 454 and 456 which, in turn, extend to one primary windingcomponent of a step-down transformer represented generally at 458. Insimilar fashion, lines 460, 462 and 464 extend to another primarywinding component of transformer 452. Line 466 extending from line 464and line 460 is coupled to another primary winding component ofstep-down transformer 458.

Secondary output windings of transformer 452 are coupled via lines 470and 472 to a full wave rectifier represented generally at 474, theoutput of which is presented at line 476 in conjunction with groundlevel at line 478. Line 478 is seen connected to ground via line 480. Afilter capacitor C29 extends between lines 476 and 478. Line 476 andline 478 via line 482 extend to a regulator 484 the output of which isdirected to lines 486 and 488. The latter lines are filtered atcapacitor C30 extending between lines 486 and 478. Device 484 may beprovided as a Three-Terminal Positive 15 volt Regulator, model LM78M15CTmarketed by National Semiconductor, Inc. of Santa Clara, Calif. With thearrangement shown, the output at line 488 is a regulated positive 15volts.

The outputs of the secondary windings of transformer 458 are present atlines 490 and 492 which are directed to a full wave rectifierrepresented generally at 494. The positive output of rectifier 494 isprovided at line 496, while the negative output thereof is provided atline 498. Ground level is present at line 500. Line 496 is filtered bycapacitors C31 and C32, while line 498 is filtered by capacitor C33.Line 496 and line 502 extending from line 500 are coupled with a voltageregulator 504. Device 504 provides a regulated +5V output at line 506.Line 506 is filtered by a capacitor C34.

Now looking to the negative output, line 498 and line 508 extending fromline 500 are directed to a negative voltage regulator 510 whichfunctions to provide a regulated −5V output at line 512. Line 512 isfiltered by a capacitor C35. Device 510 may be provided as aThree-Terminal Negative 5 volt Regulator, model LM79MO5CT marketed byNational Semiconductor, Inc. (supra).

Sense antenna 118 as described in connection with FIG. 8 is a componentof a detector assembly. The cable 148 extending from antenna 118 iscoupled with a socket shown in FIG. 12C at 520. One side of antenna 118is coupled to ground as represented at line 522 extending from socket520, while the opposite side is coupled with input line 524. Input line524 extends to the drain of MOSFET transistor Q5. The source terminal ofdevice Q5 is coupled via line 524 to the source of another MOSFETtransistor Q6. The drain of transistor Q6 is coupled with line 526. Notethat transistors Q5 and Q6 are coupled in complimentary fashion. Thesetransistors are normally in an off-state and function to block anyexcitation energy generated from excitation antenna 112 (FIG. 8) whichtends to couple into the sense antenna 118. Two such transistorsinterconnected in complimentary fashion are necessitated inasmuch astheir structures incorporate an intrinsic diode function which otherwisewould pass a sinusoid half cycle. Gate drive to transistor Q6 isprovided at line 528 incorporating gate resistor R58. Simultaneous gatedrive is provided to transistor Q5 via line 530 incorporating gateresistor R59 and extending to line 528. Line 528 extends to the outputterminal of a driver circuit 532. The Vcc terminal of device 532 iscoupled with earlier-described power supply input line 488 while its Veeterminal is coupled via line 534 to line 524 extending intermediatetransistors Q5 and Q6. Line 534 is coupled to ground through resistorR60 and filter capacitors C36 and C37 are seen to extend between lines534 and 488. The C terminal of device 532 is coupled to ground asrepresented at line 536 and its input, A, terminal is coupled via line538 to the drain terminal of MOSFET transistor Q7. Device 532 may beprovided as a 2.0 Amp Output Current IGBT Gate Drive Opto-coupler, modelHCNW 3120, marketed by Agilent Corp. (supra). It is actuated to gatetransistors Q5 and Q6 into conduction upon application of the ACQUIREsignal to line 540 extending to the gate of transistor Q7. A pull-upresistor R61 couples line 540 to +5V. Transistor Q2 is configured suchthat its source is coupled to ground as represented at line 542 and itsdrain terminal is coupled through pull-up resistor R62 to +5V. TheACQUIRE signal is derived as represented at line 411 in FIG. 12A and isasserted under the control of PLD 340 (FIG. 11F) following about a twomicrosecond delay which, in turn follows the one microsecond excitationof excitation antenna 112 (FIG. 8). With the arrangement shown, line 538is normally retained in a high logic condition to retain transistors Q5and Q6 in an off condition. Application of the ACQUIRE signal to thegate of transistor Q7 draws line 538 to the ground and effects a gatingon of transistors Q5 and Q6. As these transistors conduct, a senseantenna output signal is conveyed along line 526 where it is treated bythe low pass component of a bandpass filter network. These initial lowpass components are represented generally at 544 and are comprised ofcapacitors C38 and C39 and resistors R63 and R64. Line 526 extends tothe positive input of a bipolar amplifier 546, which is configured withfiltering capacitors C40-C45 and provides an output at line 548. Thegain of device 546 is established at resistors R65 and R66 and itsoutput then is submitted to a high pass filter stage representedgenerally at 550 and comprised of capacitor C48 and resistor R67.Capacitor C48 further functions to remove any d.c. term. Nextencountered resistor R70 provides noise suppression and line 548 is seento be coupled to the positive terminal of bipolar amplifier 552.Amplifier 552 is configured with filtering capacitors C49-C55 and itsgain is established by resistors R71 and R72. The output of device 552at line 554 extends though a low pass filtering stage representedgenerally at 556 and comprised of resistor R73 and capacitor C56. Nextin the treatment sequence is a line driver 558. Configured withfiltering capacitors C57 and C58 device 558 may be provided as anUltra-High-Speed, Low-Noise, Low-Power, Open-Loop Buffer, modelMAX4201ESA, marketed by Maxim, Inc. of Sunnyvale, Calif. The output ofdevice 558 at line 560 is protected as represented at line 562 anddevice 564. In this regard, device 564 may be an SCR/Diode Array for ESDand Transient Over-Voltage Protection model number SP724AH, byLittelfuse, Inc. (supra). Line 560 is seen to extend to a BNC connector566 which functions to connect with data acquisition components of thesystem. As noted above, the bandpass filtering will permit signal entryinto the data acquisition system of from about 100 kHz to about 2 MHz.Resonant frequencies above the latter value tend to lack sufficientpersistence beyond the interval of excitation activity. However, withimproved circuit performance, the upper range, in particular, may beexpanded.

Referring to FIG. 13 a process flow diagram of the system at hand is setforth. Looking to the figure, the process commences as represented atblock 570 wherein the practitioner and the controller componentsactivate a system START logic. Then, as represented at arrow 572 andblock 574, the high voltage ENABLE function is activated. That signal isasserted, as described earlier herein in conjunction with lines 368 and262. With the enablement of the switched power supply 226, asrepresented at arrow 576 and block 578 a determination is made as towhether the switched power supply has developed sufficient voltagelevel, for example, about 1000 volts. Where that is the case, then asrepresented at arrow 580 and block 582 a variety of interlock checks maybe carried out. For example, the antenna cables, data carrying cablesand interactive information cables must be secure. Where the system isthus correctly configured, then as represented at arrow 584 and block586 PLD 340 (FIG. 11F) derives a STATUS_OK signal which, as representedat arrow 588 is conveyed to the controller of the system. Thatcontroller, then as represented at arrow 590 and block 592 conveys aSTART or START_FRAME signal to the system as described in connectionwith line 414 in FIG. 12B. That START_FRAME signal is directed to PLD340 (FIG. 11F) which, in turn, develops the excite or FD signal whichfunctions to apply a broad spectrum pulse to excitation antenna 112(FIG. 8). As represented at arrow 594 and block 596, this broad spectrumhalf cycle pulse will have a duration of about one microsecond and willring or oscillate in the manner of a full cycle sinusoid. Accordingly,as represented at arrow 598 and block 600 the system delays for abouttwo microseconds to permit formation of the ending half cycle ofexcitation and to await its relaxation so as to minimize interferencewith the sense antenna. Following this delay, as represented at arrow602 and block 604, PLD 340 (FIG. 11F) develops an ACQUIRE signal whichfunctions to enable the detector network as described in conjunctionwith line 540 in FIG. 12A. As represented at arrow 606 and block 608 thesense network is enabled by the gating on of transistors Q5 and Q6.Sense antenna 118 (FIG. 8) then acquires the signals broadcast from theresonating heat sensor implants. As represented at arrow 610 and block612 the analog sensor signal then is submitted to low pass filter 544and, as represented at arrow 614 and block 616 the signal then issubmitted to bipolar amplification as represented at amplifier 546 inFIG. 12B. Next, as represented at arrow 618 and block 620 the analogsignal is submitted to a high pass filtering stage and any d.c. term isstripped. Following this filtering, as represented at arrow 622 andblock 624 the analog signal is again amplified as described at device552 in connection with FIG. 12B. As represented at arrow 626 and block628 the analog signal then is submitted to a low pass filter asdescribed at 556 in FIG. 12B, whereupon, as represented at arrow 630 andblock 632 the signal is introduced to line driver 558. Driver 558 thenfunctions to convey the analog signal to the data acquisition andcontrol features whereupon, as represented at arrow 634 and block 636the analog signal is sampled at an analog to digital conversion stage.As represented at arrow 638 and block 640 the digitized equivalent ofabout 32 to about 500 sample waveforms are compiled and, as representedat arrow 642 and block 644 a point-by-point averaging of those sampledigitized waveforms is carried out and as represented at arrow 646 andblock 648 the averaged waveform data is analyzed to develop resonantfrequency intensity data. The averaging of samples functions to minimizesignal noise during use of the sensors within an animal body. Typicallyabout 150 samples are averaged. In this regard, a sample may requireabout a 20 msec interval. Thus 150 samples will involve about 3 seconds,a time factor which is not long in terms of the thermal inertia of thetissue.

In general, the intensity will be of a Fourier approach wherein resonantcenter frequencies and their Fourier-based amplitudes are identified.Next, as represented at arrow 650 and block 652 controller logic isemployed to identify the above-discussed relative amplitudes of theunique resonant frequencies associated with the sensor implants.Accordingly, a unique sensor resonant frequency is determined to bepresent along with its relative amplitude and is associated with theappropriate implant identifier. In this regard, the sensors may be givena numerical identification for readout purposes. With such status andidentification data, then, as represented at arrow 654 and block 656controller interface logic is employed to develop appropriate digitaldata for providing a readout to the operator. That function isrepresented at arrow 658 and block 660. Preferably, certain of thetemperature sensor implants will have a Curie temperature at a lowerthreshold temperature, for example, 41° C., while others will be at anupper limit temperature, for example, 44° C. The readout informationwill apprise the operator as to whether temperature elevation towardthreshold and upper limit temperatures are underway and whether thethreshold temperatures have been reached or exceeded. With suchinformation, the operator is aware that thermal therapy is underway andits status.

The discourse now turns to the physical structuring of the temperaturesensing implants. Looking to FIGS. 14 and 14A, a temperature sensingimplant is represented generally at 670. Implant 670 includes a ferritecore 672 disposed symmetrically about a core axis 674. Core 672 isselected having a Curie temperature exhibiting a desired transitionrange extending to an elected temperature. Such ferrite cores aremarketed, for example, by Ceramic Magnetics, Inc., of Fairfield, N.J. Ina preferred embodiment, disposed over the outward surface of ferritecore 672 is an electrically insulative polyimide internal sleeverepresented generally at 676. Note that the oppositely disposed ends oredges of sleeve 676 as at 678 and 680 extend axially beyond thecorresponding end surfaces 682 and 684 of core 672 to provide supportfor mounting the ferrite core/sleeve subassembly on an conduction coilwinding apparatus. Alternately, the coil may be wound directly onto theferrite core by securing both ends of the core in the induction windingapparatus. The end surface 682 and 684 optionally may be trimmed off,for example, with a scalpel blade prior to further assembly steps. Woundover internal sleeve 676 are the inductive winding turns defining theinductive component of the implant. Winding 686 commences with anaxially extending lead portion 688, the tip 690 of which is bent at a90° angle to provide for electrical contact with the axially disposedside 692 of a capacitor 694. The opposite end of the winding 686 extendsaxially beneath the winding wrap to a tip 696 (FIGS. 14B, 14C). Tip 696is bent to define a right angle and is electrically coupled with theaxially disposed side 698 of capacitor 694. Windings 686 are retained inposition by an epoxy adhesive which is biocompatible for long-termimplant within the human body, e.g., Epo-Tek 301 manufactured by EpoxyTechnology, Billerica, Mass. Disposed over the assembly of ferrite core,internal sleeve, inductive winding and capacitor is an electricallyinsulative polyimide outer sleeve 700. Note that the end 702 of sleeve700 extends beyond capacitor 694. Similarly, outer sleeve end 704extends beyond internal sleeve 676. Assembly is completed by potting orfilling the voids within sleeve 700 with the noted biocompatible epoxyadhesive. That epoxy adhesive is represented at 706 in FIG. 13A. As afinal step in the implant fabrication process, its outer surfaces may becovered with a biocompatible coating represented at 708. Coating 708 maybe provided as a Parylene C (polymonochloro-p-xylylene) coating ofthickness ranging from about 0.00025 inch (0.00064 mm) to about 0.010inch (0.254 mm) and preferably between about 0.0005 inch (0.012 mm) andabout 0.001 inch (0.025 mm). These coatings are available fromorganizations such as Specialty Coating Systems, of Indianapolis, Ind.

Practitioners may find it beneficial to structure the implants as at 670with an anchoring feature engagable with surrounding tissue to preventany migration of the implants once implanted. One approach to providingsuch an anchoring structure is to extend the outer sleeve 700 beyond theoutward surfaces of the epoxy potting material 706 and associatedbiocompatible conformal coating. For example, an outer sleeve 700extension is represented in phantom at 714 in FIG. 14A extendingoutwardly from implant end surface 716. Similarly, extension of sleeve700 is shown in phantom at 718 extending axially outwardly from implantend surface 720.

A variety of anchoring structures and techniques are employable with theimplants at hand. FIG. 14 illustrates a resilient wire anchor 722 inphantom formed, for example, of a medical grade type 316 stainlesssteel. Anchor 722 is retained against the outer sleeve and associatedconformal coating during an insertion or implantation procedure. Whenreleased from the implanting tool, the anchor will spring outwardly toengaged tissue. Other anchoring approaches are described in U.S. patentSer. No. 10/246,347 (supra).

Temperature sensing implants as at 670 which are configured to identifylower threshold tissue temperatures may be combined with auto-regulatingferrite core based heater implants. Those ferrite core heater implantswill be configured to exhibit a Curie temperature, for example, at anupper limit value above the lower threshold value. A physicalstructuring of such an auto-regulated heater implant is illustrated inconnection with FIGS. 15 and 15A, 15B. Looking to those figures, theheater implant is represented generally at 730. Device 730 is formedhaving a cylindrically shaped ferrite core 732. Core 732 will exhibit aCurie temperature at an elected upper temperature limit value.Preferably, the ferrite core with exhibit a narrow Curie transitionrange as discussed above in connection with FIG. 5. Core 732 issurmounted by a cylindrical medical grade stainless steel sheath or tube734. The internal diameter of sheath 734 is slightly greater than theouter diameter of cylindrical ferrite core 732 to facilitate themanufacturing procedure. Accordingly, a slight gap of annulusconfiguration is represented at 736. Note that the ends of sheath 734 at738 and 740 extend outwardly along central axis 742 from the respectiveend surfaces 744 and 746 of ferrite core 732. The spaces defined bythese stainless steel sheath extensions is filled or potted with anepoxy adhesive as described above which is biocompatible for long-termimplant within the human body. This epoxy, in addition to filling theoutboard regions, also migrates within the gap 736. When so constructed,the entire implant 730 is coated with a biocompatible conformal layer748 layer such as the earlier-described Parylene. The heater structuresas at 730 also may be configured with a tissue anchoring feature asdescribed, for example, in connection with FIGS. 14, 15C and 15D. Intheir general operation, the heater components are inductively excitedto evoke circumferentially developed currents which effect Joulianheating at monitored temperatures below the elected Curie temperature.See generally publication (9) above.

Biocompatible stainless steel heater collars or end caps can also becombined with extended ferrite cores within thermal sensing implants asat 670. However, such an arrangement generally is not recommendedinasmuch as the temperature sensing components of the implant will beinfluenced by the Joulian heating of the heater sheaths, as opposed tothe more appropriate responsiveness to surrounding tissue temperature.Combined ferrite-based temperature sensing and heater components aredescribed in detail in the noted application for U.S. patent Ser. No.10/246,347.

Another anchor structure which may be employed with either temperaturesensing implants as at 670 or auto-regulated heater implants as at 730is represented in FIGS. 15C and 15D. Inasmuch as the heater implantcomponent shown in these figures is identical to that described in FIGS.15, 15A and 15B the same identifying numeration is employed but inprimed fashion. For this anchoring embodiment, a nonmagneticbiocompatible somewhat expanded helical spring 750 is embedded withinthe epoxy mass 748′. In this regard, the base 752 of the spring 750 isground so as to remain perpendicular to axis 742′ and the end of thespring at 754 is cut square. In general, the epoxy embedded region ofthe spring 750 may be configured with three coils more closelycompressed, for example, having a length of about 0.050 inch and maythen integrally extend to tissue engaging two coils within an axiallength of about 0.120 inch. Anchor 750 may be formed of a nonmagneticstainless steel such as a Type 316 having a diameter ranging from about0.1 mm to about 0.35 mm and preferably between about 0.15 mm to about0.25 mm.

The implants described in conjunction with FIGS. 14 and 15 may bepositioned in target tissue utilizing a variation of syringe-hypodermicneedle technology. FIGS. 16 and 17 schematically represent one approachto implantation employing such technology. Radiographic, stereotactic,ultrasound or magnetic resonant imaging guidance methods or palpationare procedurally employed to position an implant within a target tissuevolume. Of particular interest, the implants may be positionedintraoperatively as an aspect of open surgical procedures. For instance,a common approach to the treatment of cancer is that of tumor excision.Certain cases, for example, involving colorectal cancer will, upongaining access to the abdominal cavity, reveal a substantiallyinoperative metastasis of the disease. Under such circumstances thesurgical procedure typically is altered to a palliative one, forexample, unblocking the colon and/or the incision is closed and othertreatment modalities are considered.

However, with the instant system and method, the surgeon is given anopportunity for deploying hyperthermia-based temperature monitoringand/or heater implants by direct access. Of special interest, colorectalcancers tend to metastasize through the lymph system. Accordingly, theimplants can be intraoperatively positioned within lymph nodes toprovide for the induction of HSPs at the node-retained cancer cells.Other sites of tumor similarly can be implanted. Following surgicalclosure, the hyperthermia therapy procedures described herein can beundertaken in mitigation of the metastasis. In general, practitionersemploying the method herein described with respect to hyperthermia willelect to implant the most or more accessible target tissue volume.

A target tissue volume is represented in FIGS. 16 and 17 at 780internally within the body 782 of a patient. The syringe-type insertiondevice represented generally at 784 is percutaneously orintraoperatively inserted within the body 782, piercing the skin wherecalled for by virtue of the presence of a sharp tip 786. Needle 786 isfixed to a barrel or finger graspable housing 790 and removably retainsan elongate implant 792 within its internal core proximally from the tip786. Immediately behind the implant 792 within the needle 788 is aplunger rod 794, the lower tip of which at 796 is in free abutmentagainst the outwardly disposed end of implant 792 and which extendsupwardly to a plunger handle 798. As is revealed, particularly withrespect to FIG. 16, once the sharpened tip 786 of the needle 788 hasbeen properly positioned with respect to the target tissue volume 780,then plunger rod 794 and associated handle 798 are stabilizedpositionally with respect to the body 782 and target tissue volume 780,whereupon housing 790 is retracted outwardly to the orientation shown at790′ in FIG. 17. This maneuver releases implant 792 at an appropriatelocation with respect to the target tissue volume 780. Implantationdevices are described, for example, in U.S. Pat. No. 6,007,474.

Upon the determining of the boundaries or periphery and thephysiological state of a target tissue volume, the practitioner willdetermine the number of implants called for and their positioning withinthe localized tissue region. In effect, the location of the implants canbe mapped such that their resonating responses or lack thereof may beutilized in conjunction with the map to adjust the aiming feature of theexternal heating system. Referring to FIG. 18, the periphery of a targettissue volume is schematically represented at 800. Within this tissueperiphery 800 there are located twelve implants. In this regard, thoseimplants labeled A1-A6 may be temperature sensing implants havinginductors with a Curie temperature core establishing identifiable centerfrequency resonance at monitoring temperatures up to, for example, aCurie temperature of 40° C. As that Curie temperature is approached therelative amplitude of the center frequency will diminish. However, thesecond interspersed grouping of implants as at B1-B6 will incorporateinductors with cores exhibiting a Curie temperature of, for example, 43°C. Accordingly, implants B1-B6 will continue to resonate until thetissue volume within periphery 800 approaches 43° C. During that Curietransition range the relative amplitude of the analyzed resonant centerfrequency will diminish. Accordingly, the practitioner will strive toassure that implants A1-A6 are not resonating in the presence of aresonating output at implants B1-B6. In another embodiment of theinstant system and method, for example, implants B1-B6 may beauto-regulating heater devices as described above having a Curietemperature at the noted 43° C. while implants A1-A6 remain as lowerthreshold temperature sensors having inductors with cores exhibiting aCurie temperature of 40° C.

Referring to FIG. 19, a somewhat basic implementation of the system andmethod at hand is schematically represented. In the figure a patient isrepresented at 802 in a supine position on a support 804. Support 804 isformed of a material such as a polymer permitting excitation energy tobe broadcast therethrough. A target tissue volume within the body ofpatient 802 is schematically represented at 806 having a distribution ofimplants as described in connection with FIG. 18. For instance, six ofthe implants may be lower threshold temperature sensors which willresonate at temperatures approaching a Curie temperature of, forexample, 40° C. The second grouping of six sensors will be structured toresonate at monitor temperatures approaching an upper limit value, forexample, a Curie temperature 44° C. Located below the support 804 and ata location effective to cause the development of resonant outputs fromthe sensor implants is an excitation antenna 808 which is depicted ashaving a cable connection 810 with an excitation electronics assemblyrepresented at block 812. Excitation electronics assembly 812 isconfigured for interactive communication with a receiver electronicsassembly shown at block 814 as represented at dual dashed arrows 816.Arrows 816 may, for instance, be representative of opto-isolatedcommunication lines. Control to excitation electronics assembly 812 andreceiver electronics assembly 814 is represented by arrow 818 and acontroller as represented at block 820. A sense antenna is representedschematically at 822. Antenna 822 may be flexible and essentiallyconform over or drape over the patient 802 in surrounding relationshipabout target tissue volume 806. The data acquisition and analysiscomponents of controller 820 communicate as represented at arrow 824with a readout schematically represented at 826. Readout or userinterface 826 includes an on/off switch 828 and a measurement frequencyinput switch 831. The upper readout of device 826 at 830 includes anindicator apprising the operator of the lower threshold temperatureelected for the therapy as represented at 832. In this regard, theindicator 832 shows a temperature of 40° C. as being the Curietemperature of the inductor component ferrite core of six implants.Below the indicator 832 are two linear arrays of visibly perceptiblereadouts implemented, for example, as light emitting diodes (LEDs). Theupper array of LEDs is represented at 834 and is configured with sixblue output LEDs each associated with a number which will be illuminatedin the presence of monitoring temperatures below and approaching 40° C.,i.e., below Tmin. As shown by the numeric sequence of identifiersimmediately above the LEDs of array 834, each LED is assigned to beilluminated in the presence of the select resonant center frequency of agiven unique implant now numbered 1-6. Below LED array 834 is an LEDarray 838 comprised of six spaced apart green LEDs corresponding withthe numeric array 836 and configured to be illuminated when theircorresponding implant will have reached the elected relative amplitudeof the processed counter frequency data at a temperature approaching thelower threshold Curie temperature of, for example, 40° C. Accordingly,the green LEDs of array 838 are illuminated when their correspondingsensor implants are above the lower threshold temperature value of 40°C. and are not illuminated at monitor temperatures below that value.

A lower readout 840 is configured in the same manner as readout 830.Lower readout 840 includes a Curie temperature indicator 842representing the programmed upper limit Curie temperature for theremaining six implants, for instance, 43° C. Each of the upper limitimplants will have a unique resonant frequency when interrogated atmonitor temperatures below 43° C. and those unique resonant centerfrequencies will provide relative amplitude data of diminishing value attemperatures approaching that upper limit value. Lower readout 840incorporates six yellow LED implemented visual readout componentsrepresented at linear LED array 844. LEDs within the array 844 willilluminate in a yellow coloration at monitor temperatures below andapproaching the upper limit of 43° C., i.e., below Tmax. Each LED willbe illuminated when its associated implant is resonating at itsdesignated unique center frequency in the presence of monitoringtemperatures below the upper limit temperature, i.e., below Tmax.Aligned below LED array 844 is a red LED array represented generally at848. As before, each of the red indicators within array 848 isassociated with a numerically assigned implant identifier as at numericsequence 846. The LEDs at 848 will be illuminated at monitortemperatures above or closely approaching the upper limit temperature,for example, of 43° C. Above that temperature any so thermallyinfluenced implant will cease to provide the assigned unique resonantcenter frequency.

The system of FIG. 19 is quite basic and thus calls for activeparticipation on the part of the practitioner or operator. That operatoror practitioner is represented at block 850 providing controls tocontroller 820 as represented at arrow 852 and interacting with thereadout or interface 826 as represented at dashed arrow 854.

The type of heater unit employed with the instant arrangement is onewhich employs broadcast frequencies which are non-interfering with thefrequency band employed with the temperature sensing implants at hand.In this regard, the heater unit will operate at frequencies above, forinstance, 2 MHz. Such heaters, for example, are employed to carry outthermotherapy by applying microwave, radiofrequency or ultrasonic energyfrom a variety of antenna components, for example, phased arrayantennae. Such products are marketed, for example, by BSD MedicalCorporation of Salt Lake City, Utah.

For the instant demonstration operator 850 is shown providinginteraction with a heater control function as represented at arrow 856and block 858. Control 858, in turn, as represented by arrow 860 andblock 862 provides control to such an above-described non-interferenceheater unit. The output is represented at arrows 864-866. The latterarrows extend to blocks 868 and 870 representing antennae of such afocused heating system.

As is apparent, the operator 850 will wish to effect control of theheater unit 862 such that LED array 834 is off, and array 838 is on atupper readout 830, while LEDs of array 844 of the lower readout 840 areilluminated and the LEDs of arrays 848 are off. Accordingly, theoperator adjusts to maintain green and yellow LED excitation.

Looking additionally to FIG. 20, the thermal performance of thearrangement of FIG. 19 is schematically plotted. In this regard, thefigure shows a time domain abscissa and a target tissue volumetemperature ordinate. As the heater unit 862 is turned on, thetemperature of the target tissue volume 806 will gradually increase asrepresented by plot component 872. During this interval, the blue LEDindicators at array 834 will be illuminated as the target tissuetemperature is below the lower temperature threshold level Tmin asrepresented at horizontal dashed line 874. When the temperature level874 is approached, i.e., falls within the Curie transition range with aprogressive diminution is the processed relative amplitude representingan assigned resonant center frequency, the LEDs of array 834 will turnoff, while those at array 838 will turn on with the noted green color.Typically a relative amplitude diminution by a factor greater than 2(ratio of 0.5 or less) will trigger the LED performance. Resonant centerfrequencies of the lower threshold based implants at temperatures abovetheir Curie temperatures will shift to a much higher resonant frequencywhich is not detected by the system. The heating control is now underthe judgment of the operator 850 with LED arrays 838 and 844 beingilluminated. During this thermotherapy period of time there may beexcursions toward the upper limit target tissue temperature, Tmax asrepresented at plot component 876 and dashed horizontal line 878. Asthis temperature is approached, pertinent ones of the implants willexhibit a diminution of the processed relative amplitude representingtheir resonant center frequency and certain or all of the red LEDswithin array 848 will illuminate. The operator then asserts control overthe heater unit 862 to effect a lowering of the target tissuetemperature as represented by plot component 880 and this sequence ofevents may continue for the interval of therapy as represented bysubsequent plot components 882, 884 and 886. With the advantage of thepredictable relative amplitude at center frequencies practitionersshould be able to operate the system at hand such that the temperaturesremain above Tmin at level 874 and below Tmax at level 878.

Referring to FIGS. 21A-21G a procedural block diagram is presentedcorresponding with the basic system described in connection with FIGS.19 and 20. In this regard, operator or practitioner involvement isaccentuated and non-interfering heater units, for example, in theultrasound region are employed. Additionally, the procedure looks tothermal therapy, which includes not only hyperthermia therapy but alsohigher level temperature thermal therapy leading to cell necrosis. Thediagram set forth in the figures considers looking to hyperthermiatherapy with HSP induction.

Looking to FIG. 21A, the procedure commences as represented at startnode 890 and line 892 extending to block 894. Block 894 provides for theelection of target therapy temperatures for hyperthermia with aconsideration of HSP induction and a susceptibility to adjunct therapysuch as radiation therapy or chemotherapy. Then, as represented at line896 and block 898, implant sensors are selected based upon thethermotherapy goals. For the instant demonstration, the practitionerwill consider the lower threshold temperature and the upper limittemperature levels. As represented at line 900 and block 902, thepractitioner next accesses the target tissue imaging data concerning itslocation, size and any thermal response attributes such as the degree ofvascularity which the tissue may have. With that data, as represented atline 904 and block 906 the practitioner develops a preliminary placementpattern map with an identification of the sensors with respect to theirresonant center of frequency signatures. In this regard, as representedat line 908 and block 910 the temperature sensor implants are selectedand compiled for ex-vivo testing assuring the presence of a uniqueresonant center frequency at monitoring temperatures which aretemperatures considered to be below the Curie temperature of theirinductor component ferrite core members. Then as represented at line 911and block 912 (FIG. 21B) the data acquisition and control features areloaded with the resonant frequency information and numerical sensorimplant identification. Those components of the control assembly arereferred to as an interrogation assembly. With that data loaded, then asrepresented at line 914 and block 916 the control assembly orinterrogation assembly is operated to carry out an ex-vivo pre-testingof the temperature sensor implants for their resonant center frequencyperformance. This ex-vivo testing then provides for the determinationmade as represented at line 918 and block 920. Harkening to FIG. 19, andassuming six lower threshold and six upper limit implants are employed,then the blue LEDs of array 834 should be illuminated as well as theyellow LEDs of array 844. In the event that one or more of these LEDs isnot illuminated, then as represented by return line 922, the procedurereverts to line 908 and reselection of implant sensors.

Where the test posed at block 920 is affirmative and all implants areoperational, then as represented at line 924 and block 926 a heatingsystem is elected which performs at frequencies not interfering with theimplant interrogation procedure. As represented at line 928 and block930 an initial or starting heating level for the heating unit electedthen is selected. This level may or may not be adjusted in the course oftherapy. In this regard, as represented at line 932 and block 934 thepractitioner determines what the maximum interval should be to reach thelower threshold temperature at the target tissue volume. This isreferred to as the maximum warm-up interval, t_(wu). Correspondingly, asrepresented at line 936 and block 938 FIG. 21C), the practitionerdetermines what the total therapy duration should be. In this regard, aquanta of heat energy is to be administered to the target tissue volumeas determined by the intensity level of the heating unit and theduration of thermal energy application at temperatures above Tmin.

With the above basic procedures being completed, as represented at line940 and block 942 a general or local anesthetic agent is administeredand, as represented at line 944 and block 946 the practitioner employsultrasound, stereotactic systems, upright mammographic guidance orpalpation to insert the sensor implants into the target tissue volumeusing an appropriate delivery device as generally discussed inconnection with FIGS. 16 and 17. Placement of the implants is made inaccordance with the preliminary placement pattern or map. It isrecommended that the skin of the patient be marked to indicate theclosest location of the implants for purposes of focusing the heatingunit. Following implantation, as represented at line 948 and block 950 aquery is made as to whether the implants are in their correct positions.In the event that they are not, then as indicated at line 952 theprocedure reverts to line 944 for purposes of carrying out correctpositioning. Where the implants are in appropriate locations then asrepresented at line 954 and block 956 the practitioner revises theplacement pattern map if necessary. Additionally, as represented at line958 and block 960 the practitioner records the skin-carried markerlocation for future reference as well as records all resonantfrequencies and associated sensor identification numbers with respect tothe placement pattern map.

It may be recalled that these tetherless implants will remain in placeindefinitely and that the patient typically will undergo severaltherapeutic sessions. Accordingly, it is necessary that the implantinformation be recorded. Thus, the next line 962 is shown leading totherapy session procedures as labeled. Each of these procedurescommences as represented at line 964 extending to block 966. At block966, the practitioner reproduces the skin-carried markers if necessary.Next, as represented at line 968 and block 970 the patient is positionedupon a treatment fixture such as a table or chair such that the skinsurface carried markers are clearly visible. Then, as represented atline 972 and block 974, guided by the skin-carried marker, thepractitioner positions the heating assembly output component, forexample, phased array antennae as close as practical to the targettissue volume. Additionally, as represented at line 976 and block 978,again guided by the skin-carried marker, the practitioner positions theexcitation and receiver or sense antennae as close as practical to thetarget tissue volume. In this regard, the sense antenna may be flexibleand, in effect drapes over the body surface of the patient.Additionally, where necessary, as represented at line 980 and block 982all of the recorded unique resonant center frequencies and associatedsensor identification numbers are loaded into the interrogation assemblycontroller or data acquisition system. That interrogation controllerthen is turned on as represented at line 984 and block 986 and theprocedure continues as represented at line 988 to the query at block990. At this time, a determination is made as to whether all appropriatelower threshold and upper limit implants are resonating in response tomonitoring or body level temperature, for example, with respect to FIG.19 a determination is made as to whether the appropriate LEDs withinarray 834 are illuminated as well as the LEDs within array 844. If theyare not, then as represented at line 992 and block 994 the practitioneragain consults the implant map and carries out adjustments of the exciteand sense antennae. The test at block 990 then is reiterated asrepresented at line 996 extending to line 988. Where the interrogationsystem is performing appropriately, then as represented at line 998 andblock 1000 (FIG. 21E) the heating assembly is activated with thepredetermined initial heating power level and, as represented at line1002 and block 1004, a time-out of the maximum warm-up interval, t_(wu)commences. Next, as represented at line 1006 and block 1008 a check isnext made as to whether all appropriate LEDs of arrays 838 and 844 (FIG.19) are illuminated. In the event they are not, then as represented atline 1010 and block 1012 a determination is made as to whether themaximum warm-up time has timed out. In the event that it has not, theprocedure continues as represented at line 1014 to the query posed atblock 1016 again determining whether the LED arrays 838 and 844 areappropriately illuminated. In the event that they are appropriatelyilluminated, the procedure continues as represented at line 1018.

Returning to block 1008, in the event that all appropriate LEDs of thearrays 834 and 844 are illuminated, then the procedure continues asrepresented at line 1020 extending to line 1018. Where the query posedat block 1012 indicates that the maximum warm-up time has been timedout, then as represented at line 1022 the program reverts to node A,which reappears in FIG. 21F. Looking to the latter figure, line 1024extends from node A to block 1026 providing for practitioner adjustmentof the heating assembly output component position and/or the heatingpower level. Then, as represented at line 1028 the program reverts tonode B which reappears in FIG. 21E in connection with line 1030extending to line 1006.

Returning to the query posed at block 1016, where LED array 838indicates that the target tissue volume temperature is above the lowerthreshold temperature, Tmin and below the upper limit temperature asrepresented at LED array 846, then the program continues as shown atline 1018 to block 1034 representing the commencement of a session of apredetermined therapy duration. That therapy duration commences to betimed out. Where proper therapy temperatures are not present, theprocedure reverts to node B a represented at line 1032. The programcontinues as represented at line 1036 leading to the query posed atblock 1038 (FIG. 21G) where a determination is made as to whether any ofthe upper limit temperatures has been exceeded as indicated by anillumination of one or more LEDs within the LED array 848 (FIG. 19). Inthe event any such temperature elevation excursions have occurred, thenthe procedure reverts as represented at line 1040 to node A providingfor the carrying out of adjustment of the heating assembly outputcomponent or components and heating power level. In the event of anegative determination with respect to the query posed at block 1038,then as represented at line 1042 and block 1044, a determination is madeas to whether the therapy duration has timed out. In the event that ithas not timed out, then the procedure reverts as represented at line1046 to line 1036. Where the therapy duration has timed out, then asrepresented at line 1048 and block 1050 the heating assembly or unit andthe interrogation assembly or controller are turned off and, asrepresented at line 1052 and block 1054, all therapy data are recordedand as represented at line 1056 and node 1058 the therapy session isended. As noted above, in general, several therapy sessions will beinvolved in carrying out a complete treatment. The untethered nature andessentially permanent positioning of the implants beneficiallyfacilitates the carrying out of several therapy sessions.

Where auto-regulating heater implants as described in connection withFIGS. 15 and 15A-15D, are employed as the upper temperature limitdevices, then the heating units employed typically will be of aninductive variety. As a consequence, the electromagnetic energybroadcast by them will interfere with the interrogation equipmentemployed in accordance with the invention. Accordingly, an intermittentapproach is utilized wherein the inductive heating assembly is activatedfor a heating interval and then turned-off, whereupon the interrogationassembly is activated. Where this intermitting is carried outautomatically as opposed to the basic system of FIG. 19, then, forinstance, the heating assembly may be enabled for about 100 millisecondsto about 1000 milliseconds and the interrogation assembly then isenabled for a sequential 10 milliseconds to about 100 milliseconds. Thisprovides for almost continuous noise-free interrogation and the offinterval for the heating assembly permits a modicum of accommodation forthermal inertia-based “overshoot” which may be encountered.

A further effect of the noted inductive interference has been describedin connection with FIG. 5. It may be recalled in that figure that with ahigh magnetic field intensity applied to the sensors or auto-regulatingheaters, the Curie transition range will soften. However byintermitting, the original transition range of the sensors essentiallyis maintained.

A graphic illustration of the intermitting performance of the system isprovided in connection with FIG. 22. Referring to that figure, it may benoted that the graph is sectioned in terms of time along its abscissa,while power applied to the target tissue volume and, in particular, tothe heater implant is represented along a left ordinate. The noted poweris seen to be identified along ordinate 1066 as extending in valueessentially from zero to an initial applied power P_(a) at an initialpower level represented at dashed line 1068. While shown in horizontalfashion, the level 1068 may vary in accordance with power adjustments.The temperature witnessed by the sensor implants and/or heater implantsis shown at ordinate 1070 extending from body temperature T_(body) to alower threshold temperature, Tmin, represented at dashed line 1072 aswell as to an upper limit temperature, Tmax represented at dashed line1074. Related permeability of the core components of the implantedtemperature sensors and/or implanted heaters is represented alongordinate 1075 as extending from μ_(MIN) (unity value for relativepermeability) and extends to generally starting relative permeabilitywhich may fall within a substantial range, for example to values ofabout 100 to about 10,000. A maximum relative permeability level, μ_(N)for the given sensor at hand is represented at dotted horizontal line1076, while the relative permeability of the ferromagnetic corecomponent of the sensors or heaters is represented at dashed curve 1078.Leftward ordinate 1080 extends as an arrow having a dashed uppercomponent representing diminished intensity, DI of the sensor output ata stable resonant center frequency as temperature approaches Curie pointtemperature within the Curie transition range. Recall that control isbased upon the corresponding relative amplitudes. The arrow extends tolower threshold temperature, Tmin. That ordinate extends upwardly indashed form at 1082 to represent the substantial resonant frequencyshift should Curie temperature be reached for the lower threshold.Implants having a Curie temperature corresponding with the upper limitlevel 1074 identified as Tmax are represented at the arrow 1084 having adashed upper component representing diminished intensity, DI of thesensor output at a stable resonant center frequency as temperatureapproaches Curie point temperature with the Curie transition range.Should level 1078 be reached, then the resonant frequencies of upperlimit temperature sensor components will shift substantially upwardly invalue as represented at dashed line 1086.

Now considering the intermittent activation or duty cycle-definedapplication of power and activation/enablement of the interrogationcomponents, it may be observed that power is represented as initiallybeing applied as shown at power curve 1088 between times t₀ and t₁,representing a power application increment of time δt₁. Following thispower application interval the heating function is turned off for asensing or interrogation time extending between times t₁ and t₂,representing an increment of measurement or sensor interrogation time,δt₂. Because the electromagnetic field applied for sensor interrogationpurposes is relatively low in power, the Curie transition rangecharacteristic elected for the sensors remains quite stable. Recall thediscussion associated with FIG. 5, Note that during the intervals, δt₁and δt₂ the temperature value of the implanted sensor as indexed alongordinate 1070 and shown at dashed curve 1090 commences to rise and isseen to exhibit a modicum of thermal inertia during interrogationinterval δt₂. This power-on-power-off-interrogation sequence continues,for example, a power-on condition being applied between times t₂ and t₃with an interrogation interval occurring between times t₃ and t₄. Asthese power-on and interrogation intermitting cycles continue, curve1090 is seen to rise, eventually approaching the lower thresholdtemperature, Tmin at dashed horizontal line 1072. For illustrativeconvenience, note that the figure is broken following time t₅. Power isindicated as being applied during the heating interval t_(n) to t_(n+1).At the termination of that power application time interval, tn+1, lowerthreshold Curie temperature is approached or achieved at the implantsensor inductor core component and may produce a slight thermalovershoot at 1092 within the acceptable range of temperatures betweendashed lines 1072 and 1074. Note, as this occurs, that a permeabilitycurve for the lower threshold sensor implants at knee 1094 change ofstate is experienced and the relative permeability of the implantedsensor component for this lower threshold drops dramatically essentiallyto a unity value as represented at curve 1078 inflection point 1096occurring at time t_(n+2). Under the ensuing time element, unless thetemperature being sensed by the lower threshold devices drops, forexample, below the lower threshold at dashed line 1072, the relativepermeability of the core of the sensor will remain at a unity level asrepresented at 1098. Should the temperature being sensed by the lowerthreshold component drop in temperature below the lower threshold atdashed line 1072 as represented at point 1100, then as shown atpermeability curve portion 1102, relative permeability abruptly rises,for example, to level 1104. Should the lower threshold temperaturesensor again experience a drop in temperature below the threshold level1072 then as represented at curve portion 1106 relative permeabilityagain will abruptly change toward unity. Assuming that the temperatureremains elevated, the unity value for relative permeability for thelower threshold sensor components will remain at a unity level asrepresented at curve portion 1107. Should the heating unit cause thetarget tissue volume approach or to exceed the upper limit temperatureTmax as represented at point 1108 then a power adjustment is called forto return the temperature to its proper range as represented at curveportion 1110. This results in a lowering of the power applied, Pa′, asrepresented at dashed level 1112.

Referring to FIGS. 23A-23H a procedural block diagram is presenteddetailing the activities undertaken with the intermittent operation ofthe system as discussed in connection with FIG. 22. Looking to FIG. 23A,the procedure commences as represented at node 1120 and line 1122extending to block 1124. As before, the practitioner elects the targettherapy temperatures, for example, for hyperthermia and a considerationof HSP induction as well as susceptibility to adjunct therapies. Next,as represented at line 1126 and block 1128 the implants are selected forthe target therapy temperatures. As before, the practitioner willconsider a lower threshold based temperature sensing device as well asan upper limit based device. As represented at line 1130 and block 1132,the practitioner accesses target tissue imaging data concerning thelocation size and thermal response attributes of the target tissuevolume. With that information, as represented at line 1134 and block1136 the practitioner develops a preliminary implant placement patternmap with an identification of the sensors and/or auto-regulating heaterimplants. This map having been selected, as represented at line 1138 andblock 1140 the practitioner selects and compiles the sensors such as thelower threshold temperature sensors and any upper limit temperaturesensor implants to be employed. Ex-vivo testing is carried out of thetemperature sensing implants to determine that they are indeeddeveloping the appropriate resonant center frequencies at monitoringtemperatures below associated Curie point temperature. Next, asrepresented in FIG. 23B at line 1142 and block 1144 the interrogationassembly or data acquisition components are loaded with the uniqueresonant center frequencies involved and the associated sensor implantidentifications. Next, a testing of the temperature sensor implants iscarried out as represented at line 1146 and block 1148. This testdetermines whether the appropriate resonant center frequencies aredetected at room temperature. That determination is represented at line1150 and the query posed at block 1152. In effect, the test determineswhether the appropriate LEDs of arrays of 834 and 844 are illuminated asdescribed in connection with FIG. 19. In the event one or more of theseLEDs is not illuminated, then as represented at line 1154 the procedurereverts to line 1138. Where all temperature sensor implants areperforming at room temperature, then as represented at line 1156 andblock 1158 an alternating current (ACF) field heating system, forexample, an inductive system is elected and as represented at line 1160and block 1162 an initial power level is selected for the heatingsystem. Next, as represented at line 1164 and block 1166 thepractitioner determines the maximum warm-up interval, t_(wu) forinitially achieving the lower threshold minimum temperature, Tmin. Thepractitioner then determines the therapy session duration attemperatures above the lower threshold and below the upper limit asrepresented at line 1168 and block 1170 (FIG. 23C). With thisaccomplished, as represented at line 1172 and block 1174 a general orlocal anesthetic agent is administered to the patient and, as set forthat line 1176 and block 1178, the target tissue volume is analyzed usingsuch modalities as ultrasound, sterotactic, or upright mammographicguidance or palpation. The temperature sensor implants are located aswell as any auto-regulating heater implants at the target tissue volumein accordance with a preliminary placement pattern or map. Further, theskin surface of the patient's body is marked to identify the implantlocations. As represented at line 1180 and block 1182 a determination ismade as to whether the implants are in the proper location. If animplant is not properly located, then as represented at line 1184 theprocedure reverts to line 1176. With the implants being properlylocated, then as represented at line 1186 and block 1188 any revisionsto the implant pattern map are carried out and the program continues asrepresented at line 1190 and block 1192 where the skin carried markerlocation is recorded for future reference and all resonant frequenciesand associated sensor identification numbers further are recorded.

As then labeled in conjunction with at line 1193, one or more therapysessions are carried out. As noted above, inasmuch as the sensors areuntethered and essentially permanently implanted, multiple therapysessions can be carried out without a requirement for re-implanting suchdevices. As multiple therapy sessions are carried out, the skin carriedmarker may somewhat disappear. Accordingly, lines 1193 and 1194 extendto block 1195 (FIG. 23C) calling for the reproduction of the marker ifnecessary. Line 1196 and block 1198 provide for the positioning of thepatient on a table or chair such that the marker is clearly visible andproperly oriented. That marker, then as represented at line 1200 andblock 1202, is utilized in positioning the heating assembly outputcomponent with respect to the target tissue volume. Additionally, asrepresented at line 1204 and block 1206 the interrogation assemblyexcitation and receiver or sense antennae are appropriately positioned.As noted above, the sense or receiver antenna is configured as beingflexible and in effect drapes across the patient's body. From block1206, as represented at line 1208 and block 1210 if not carried outbeforehand, the practitioner loads all unique resonant centerfrequencies into the interrogation assembly controller. Then, asrepresented at line 1212 and block 1214 a test of the interrogationsystem is carried out by initially turning on the interrogation assemblycontroller and carrying out excite and sense cycles as represented atline 1216 and block 1218. A determination then is made as to whether allappropriate LEDs within arrays 834 and 844 as described in conjunctionwith FIG. 19 are illuminated. In the event that they are not soilluminated, then as represented at line 1220 and block 1222 thepractitioner consults the implant placement map and adjusts theinterrogation antennae appropriately. The procedure then returns to line1216 as represented at line 1224. Where all appropriate LEDs have beenilluminated, the procedure continues as represented at FIG. 23E and line1226 and block 1228 providing for the actuation of the heating assemblywith the initial heating ACF power level for a heating period. At thesame time, as represented at line 1230 and block 1232 timing iscommenced with respect to the warm-up time, t_(wu). At the terminationof the heating period, as represented at line 1234 and block 1236 theheating assembly is turned off and as provided at line 1238 and block1240 the interrogation controller is activated with the generation ofthe earlier-described excite and acquire signal activities. Theseactivities are carried out for an interrogation interval and followingthat interval as represented at line 1242 and block 1244 a query is madeas to whether the lower threshold LED array 838 and upper limit LEDarray as at 844 (FIG. 19) are illuminated to represent that thetherapeutic temperature range has been reached. In the event of anegative determination to this query, then as represented at line 1246and block 1248 a determination is made as to whether the warm-up time,t_(wu) has timed out. In the event that it has not timed out, then asrepresented at line 1250 and block 1252 the query posed at block 1244 isreiterated. Where these LED arrays are illuminated, the procedurecontinues as represented at line 1254. On the other hand, where all ofthe noted LEDs are not illuminated then the procedure continues asrepresented at line 1256 and node A. Note additionally, that in theevent that the warm-up time, t_(wu) indeed has timed out in connectionwith the query at block 1248, then the procedure also extends asrepresented at line 1258 to node A.

Looking momentarily to FIG. 23F, node A reappears in conjunction withline 1260 extending to block 1262 providing for manually adjusting theheating assembly output component position and/or the heating powerlevel. Next, as represented at line 1264 and block 1266, the heatingassembly is turned on for the noted heating period. As represented atline 1268, the procedure then extends to node B. Node B reappears inFIG. 23E in connection with line 1270 extending to earlier describedblock 1236 providing for turning off the heating unit power followingthe heating period.

In the event of an affirmative determination with respect to the queryposed at block 1252, then as represented at line 1254 and block 1272 thesession therapy duration time-out commences. Where the query at block1244 indicates that all appropriate LEDs are illuminated, the procedureextends as represented at line 1274 to line 1254. With the commencementof therapy duration time-out, as represented at line 1276 and block 1278the interrogation assembly is turned off and as represented at line 1280and block 1282 (FIG. 23H) intermitting continues with the turning on ofthe heating assembly for the heating period. At the termination of thatheating period, as represented at line 1284 and block 1286 the heatingassembly is turned off and as represented at line 1288 and block 1290the interrogation assembly again is activated. The procedure thencontinues as represented at line 1292 to the query posed at block 1294.Block 1294 questions whether any of the LEDs representing a temperatureexcursion above the upper limit have been illuminated, for example, theillumination of any of the LEDs of array 848 described in connectionwith FIG. 19. In the event of an affirmative determination, then asrepresented at line 1296 the procedure reverts to node C. Lookingmomentarily to FIG. 23H, node C reappears in connection with line 1298extending to block 1300 providing for turning off the heating unit. Uponthe heating unit being turned off, as represented at line 1302 and block1304. The interrogation assembly is activated and as represented at line1306 the procedure reverts to node D.

Node D reappears in conjunction with line 1308 in FIG. 23G. In thisregard line 1308 extends to line 1292 and the query at block 1294. Wherenone of the LEDs of array 848 (FIG. 19) are illuminated, then asrepresented at line 1310 the procedure carries out the query posed atblock 1312. At block 1312 a determination is made as to whether thetherapy duration has timed out. In the event that it has not, then theprocedure loops as represented at line 1314 to line 1280. Where atherapy duration has timed out, then as represented at line 1316 andblock 1318 both the heating assembly and interrogation assembly areturned off and, as represented at line 1320 and block 1322 therapy dataare recorded and as represented at line 1324 and node 1326 the therapysession is ended.

The intermitting approach also can be employed with temperature sensorimplants which respond to identify a lower temperature threshold andupper limit temperature heater implants as described earlier inconnection with FIGS. 15 and 15A-15D. Inasmuch as the heater implantstypically will require an inductive form of alternating field currentexcitation, intermitting is called for to both avoid interference withthe interrogation procedure. The procedure for carrying out thisintermitting approach with this combination of implants is provided inconnection with FIGS. 24A-24G. Looking to those figures, a procedurecommences with start node 1330 and line 1332 extending to block 1334. Atblock 1334, the practitioner elects target temperatures forthermotherapy and susceptibility to adjunct therapy such as radiationtherapy or chemotherapy. Those target temperatures will involve thenoted lower threshold sensed temperature and the upper limitauto-regulating heater temperature. Next, as represented at line 1336and block 1338 the implant sensors with lower threshold temperatures areselected as well as the auto-regulating heater implants with regulationto the upper limit temperature. Then, as represented at line 1340 andblock 1342 target tissue imaging data is accessed, such data concerninglocation, size and thermal response attributes of the target tissuevolume. As represented at line 1344 and block 1346 the practitionerdevelops a preliminary placement pattern map for the heater implants andtemperature sensor implants within the identified target tissue volume.Upon developing this map, as represented at line 1348 and block 1350 thelower threshold temperature sensing implants are selected and compiledfor ex-vivo testing with respect to room temperature. Additionally, asrepresented at line 1352 and block 1354 the unique resonant centerfrequencies to be used with respect to the lower threshold sensorimplants are loaded into the interrogation assembly and, as representedat line 1356 and block 1358 the interrogation assembly is controlled tocarry out the ex-vivo pre-testing of the lower threshold sensorimplants. This test results in the illumination of appropriate LEDs. Inthis regard, line 1360 extends from block 1358 to block 1362 wherein thequestion is posed as to whether all appropriate Tmin LEDs are on. ThoseLEDs will be, for example, within the array 834 described in conjunctionwith FIG. 19. In the event that the appropriate LEDs are not on, then asrepresented at line 1364 the procedure reverts to line 1348. Where allappropriate lower threshold temperature LEDS have been illuminated, thenas represented at line 1366 and block 1368 an ACF heating system iselected which is suitable for performance with the auto-regulatingheater implants. Such a system typically will be an inductive one. Uponelecting the ACF heating system, then as represented at line 1370 andblock 1372 the initial ACF heating power level is selected. With thatselection, as represented at line 1374 and block 1376 a maximum warm-upinterval to initially achieve the lower threshold temperature isdetermined. As represented at line 1378 and block 1380 (FIG. 24C) adetermination is made as to the length of the session therapy while thetarget volume is at or above the lower threshold temperature. With thatdetermination, as represented at line 1382 and block 1384 a general orlocal anesthetic agent is administered and the temperature sensingimplants and heater implants are located within the target tissue volumeas represented at line 1386 and block 1388. The positioning of theimplants is carried out using ultrasound, stereotactic or uprightmammographic guidance or palpation. Additionally, the patient's skin orthe exterior of the patient's body is marked to indicate the closestlocation of the implants. As represented at line 1390 and block 1392 adetermination is made as to whether the implants are in correctpositions. In the event they are not, then the procedure loops asrepresented at line 1394 to line 1386. Where a determination is madethat the implants are in their correct positions, then as represented atline 1396 and block 1398 a revision of the placement pattern map is madeif it is necessary. Next, as represented at line 1400 and block 1402 themarker location is recorded for future reference as well as all resonantfrequencies and associated lower threshold sensor identifications. Aslabeled in conjunction with line 1404 the patient is now prepared toundergo a number of therapy sessions. Lines 1404 and 1405 extend toblock 1406 (FIG. 24D) providing for the reproduction of the marker ifnecessary. Next, as represented at line 1408 and block 1410 the patientis positioned on the support such that the marker on the patient's skinis clearly observable and the target tissue volume is accessible toheating and interrogation procedures. Next, as represented at line 1412and block 1414 the heating assembly output component is positioned asclose as practical to the target tissue volume. Additionally, asrepresented at line 1416 and block 1418 the excitation and sense orreceiving antennae are located with respect to the target tissue volume.If not accomplished earlier, as represented at line 1420 and block 1422all of the unique resonant frequencies and lower threshold temperatureimplant identifiers are loaded into the interrogation assembly. Next, asrepresented at line 1424 and block 1426 the interrogation assemblycontroller is turned on and a performance of the lower thresholdtemperature sensor implants is evaluated as represented at line 1428 andblock 1430. At block 1430 a determination is made as to whether theappropriate lower threshold LEDs are illuminated. Those LEDs weredescribed in connection with FIG. 19 at array 834. In the event certainor all of those appropriate LEDs are not illuminated, then asrepresented at line 1432 and block 1434 the practitioner consults theimplant placement map and adjusts the excite and/or sense antennae asappropriate and the procedure returns as represented at line 1436 toline 1428. Where all appropriate LEDs have been illuminated, asrepresented at line 1438 and block 1440 (FIG. 24E) the heating assemblyis actuated with initial alternating current field heating power for aheating period. As the heating assembly is activated, as represented atline 1442 and block 1444 timing is commenced for the time to warm-up andthe procedure continues as represented at line 1446 extending to block1448. Block 1448 provides for turning off the heating assembly power,whereupon as represented at line 1450 and block 1452 thecontroller/interrogation assembly is turned on to carry out the exciteand acquire functions. Based upon that interrogation, as represented atline 1454 and block 1456 a determination is made as to whether the lowerthreshold heating level has been reached as determined by theillumination of appropriate ones of LED array 838 (FIG. 19). Where allappropriate such LEDs are not illuminated, then as represented at line1458 and block 1460 a determination is made as to whether the warm-uptime interval has timed out. If it has not, then as represented at line1462 and block 1464 the query posed at block 1456 is reasserted. Whereall appropriate LEDs have been illuminated the procedure continues asrepresented at line 1466 and block 1468 providing for the timing out ofthe session therapy duration. Returning to block 1456 where allappropriate LEDs have been illuminated, then the procedure continues asrepresented at line 1470 to line 1466. Where the determination at block1460 is that the warm-up time interval has expired, then as representedat line 1472 the procedure reverts to node A. Similarly, where thedetermination at block 1464 is that all appropriate LEDs have not beenilluminated the program reverts to node A as represented at line 1474.

Looking momentarily to FIG. 24F node A reappears in conjunction withline 1476 extending to block 1478. Block 1478 provides for the manualadjustment of the heating assembly output component and/or heating powerlevel. Additionally, as represented at line 1480 and block 1482 theheating assembly power is turned on for a heating period and the programcontinues as represented at line 1484 and node B.

Returning to FIG. 24E, node B reappears with line 1486 extending to line1446.

With the commencement of session therapy duration time-out asrepresented at block 1468, the procedure turns on the heating assemblyfor the noted heating period as represented at line 1488 and block 1490(FIG. 24G). Following the heating period, as represented at line 1492and block 1494 the heating assembly is turned off and as represented atline 1496 and block 1498 the controller/interrogation assembly is turnedon. The procedure then queries as to whether the session therapyduration has timed out as represented at line 1500 and block 1502. Wherethat is not the case, then as represented at line 1504 the procedurereverts to line 1488. However, where the session therapy has timed out,then as represented at line 1506 and block 1508 the heating assembly andthe interrogation assembly are turned off and, as represented at line1510 and block 1512 therapy data are recorded. With such recordation, asrepresented at line 1514 and node 1516 the therapy session is ended.

Referring to FIG. 25 the system at hand is illustrated in connectionwith a controller exhibiting more elaborate interface features. Lookingto the figure, the patient reappears at 1524 supine upon a support ortable 1526 and the target tissue volume is represented at 1528. Anexcitation antenna 1530 is located beneath patient 1524 in the vicinityof target tissue volume 1528. Antenna 1538 is operatively associatedwith the excitation electronics assembly represented at block 1532 by acable 1534. Assembly 1532, in turn, is interactively associated with areceiver electronics assembly represented at block 1538 by anopto-isolated coupling represented at arrows 1540. Receiver assembly1538 is coupled with a sense antenna 1542 by cable 1544. As before,antenna 1542 may be flexible and draped upon the surface of the patient1524 in the vicinity of target tissue volume 1528. A controller isrepresented at block 1546 which is operatively associated with receiverassembly 1538 and excitation electronics assembly 1532 as represented byarrow 1548 and the controller is interactively coupled with a controlconsole 1550 as represented at arrow 1552. A heater unit is representedat block 1554 having an output represented at arrows 1556-1558 extendingto output components 1560 and 1562. Heater unit 1554 is controlled froma heater control assembly as represented at arrow 1564, block 1566 andarrow 1568. Control 1566 is operatively associated with the console 1550as represented by arrow 1570.

Console 1550 incorporates LED arrays as have been earlier-described inconnection with FIG. 19. Accordingly, those arrays as well as theirassociated implant identifications are shown with the same numericalrepresentation but in primed fashion. An on/off switch is represented at1572 in combination with an on/off indicator LED 1574. Maximum warm-uptime is inserted by the operator into the system with up-down switches1575 in association with a time read-out 1576. Where an intermittingtype interrogate/heat operation is employed, the corresponding dutycycle is loaded into the system by actuation of up-down switches 1577 inconjunction with read-out 1578. Total therapy time also is inserted withup-down switches 1580 which are operated in association with read-out1582. A read-out 1584 provides the operator with data as to the therapytime elapsed. Read-out 1584 may be reset at reset switch 1586 and anerror/prompt display is provided at 1588. A heater unit ready green LEDis provided at 1590 and a corresponding controller ready green LEDcueing device is represented at 1592. Therapy is started by actuatingswitch 1596 and the time to reach the lower threshold temperature levelelapsing is represented by red LED cueing output 1598. At such time asthat lower threshold of heating has been achieved, therapy timing iscommenced with a green LED based cue 1600. As LED 1600 is illuminated,therapy time elapsed information at read-out 1584 is actuated. At suchtime as the therapy time elapsed 1584 is equivalent to the therapy time1582, an LED cue is provided by green LED 1602 indicating that therapyis complete. In the course of therapy, the practitioner may wish to stopthe therapy. Accordingly, a stop therapy switch 1604 is provided with anassociated red LED cue representing a stop therapy condition at 1606.

Referring to FIGS. 26A-26J the procedure associated with the enhancedsystem of FIG. 25 is set forth in block diagrammatic fashion. In FIG.26A, the procedure is shown to start at node 1612 and line 1614extending to block 1616. Block 1616 provides for the election of thetarget therapy temperatures, for example for hyperthermia with aconsideration of HSP induction as well as adjunct therapies. Followingthis election, as represented at line 1618 and block 1620, implantsensors are selected based upon the target therapy temperatures. Asbefore, this selection may include lower threshold temperature basedimplants and upper limit temperature based implants. As represented atline 1622 and block 1624 the practitioner accesses target tissue imagingdata with respect to its location, size and thermo response attributes.With that data at hand, then as represented at line 1626 and block 1628an implant placement pattern map is developed with the identification ofsensors and their proposed location within the target tissue volume.Next, as represented at line 1630 and block 1632 the sensor implants tobe utilized are selected and compiled for ex-vivo testing. For thispurpose, as represented at lines 1634 and block 1636 (FIG. 26B) theunique resonant center frequencies and identification of the sensorimplants is loaded into the control system. The ex-vivo test then iscarried out as represented at line 1638 and block 1640. As representedat line 1642 and block 1644 a test is carried out to determine that theappropriate LEDs within arrays 834′ and 844′ are illuminated. In theevent the test fails, the procedure reverts as represented at line 1646to line 1630. With an affirmative response to the query posed at block1644, then as represented at line 1648 and block 1650 a heating systemmay be elected with frequencies not interfering with the interrogationassembly. Where such interference may occur, then the intermittent formof operation of the system is called for. Next, as represented at line1652 and block 1654 the practitioner elects an initial heating powerlevel and, as represented at line 1656 and block 1568 a maximum warm-upinterval is determined. That interval is loaded into the system byactuation of up-down switch 1575 in conjunction with readout 1576 (FIG.25). As represented at line 1660 and block 1662 (FIG. 26C) the sessiontherapy duration is determined. That duration will be monitored at suchtime as the lower threshold temperature is reached. Locating theimplants then is commenced as represented at line 1664 and block 1666with the administration of a general or local anesthetic agent followingwhich, as represented at line 1668 and block 1670 the sensor implantsare positioned utilizing guidance techniques in accordance with apreliminary placement pattern and the exterior or skin of the patient ismarked to identify the closest location of the implants. Then, asrepresented at line 1672 and block 1674 a determination is made as towhether the implants are correctly positioned. In the event they arenot, then the procedure returns as represented at line 1676 to line1668. Where implant positioning is correct, then as represented at line1678 and block 1680 the implant placement pattern map is updated ifnecessary. As a final step before commencement of a therapy session, asrepresented at line 1682 and block 1684 the marker location is recordedas well as all resonant center frequencies and associated sensoridentification.

The patient is now prepared for undertaking one or many therapy sessionsas labeled in correspondence with lines 1686 and 1687, extending toblock 1688 (FIG. 26D) providing for the reproduction of the marker ifnecessary. Where therapy sessions subsequent to the initial ones are athand, then the practitioner may wish to reconsider the election of theheating unit; determination of a maximum warm-up interval; the selectionof session therapy duration; and the reloading of previously recordedunique resonant center frequencies into the interrogation assembly. Asrepresented at line 1690 and block 1692 the practitioner selects theinterrogate/heat duty cycle if an intermittent type control is at hand.That selection is made by actuation of up-down switches 1575 inconjunction with readout 1577 as shown in FIG. 25. Next, as representedat line 1694 and block 1696 the therapy time elapsed reset button orswitch 1586 is actuated. The procedure continues as represented at line1698 leading to block 1700 which provides for positioning the patient ona table or chair and appropriately orienting the marker, whereupon asrepresented at line 1702 and block 1704 the heating assembly outputcomponent or components are positioned as close as practical to thetarget tissue volume. Additionally, as represented at line 1706 andblock 1708, utilizing the marker on the patient the excitation andreceiver or sense antennae are positioned with respect to the targettissue volume. As represented at line 1710 and block 1712 the controllerthen acquires the on and continuity status of the interrogationassembly. With that information, as represented at line 1714 and block1716 (FIG. 26E) a determination is made as to whether the interrogationassembly status is ok. In the event that it is not, then as representedat line 1718 and block 1720 an error cue is presented at display 1588indicating that the antennae cables to the electronics and controlconsole are not properly attached. Additionally, as represented at line1722 and block 1724 a prompt is presented at display 1588 indicatingthat cable attachments should be checked and the procedure returns toline 1714 as represented at line 1726. Where the interrogation assemblystatus is ok, then as represented at line 1728 and block 1730 green LED1590 is illuminated. Next, as represented at line 1732 and block 1734the heating unit is actuated following which, as represented at line1736 and block 1738, the control system acquires on and continuitystatus of the heating unit and determines, as represented at line 1740and block 1742, whether that status is ok. Where that status is not ok,then as represented at line 1744 and block 1746 an error message ispresented at display 1588. Additionally, as represented at line 1748 andblock 1750 a prompt is presented at display 1588 advising the operatorto check lead/cable attachments and the procedure returns to line 1736as represented at line 1752. Where the heating unit status is ok, thenas represented at line 1754 and block 1756 green LED 1592 isilluminated. With the above checks being made, as represented at line1758 and block 1760, thermotherapy is started by actuating the “starttherapy” button or switch 1596. With this actuation, as represented atline 1762 and block 1764 (FIG. 26F) the heating underway green LED 1600is illuminated and the procedure continues as represented at line 1766to the query at block 1768 determining whether all of the appropriateLEDs of LED arrays 834′ and 844′ are illuminated, indicating thatheating is underway but that the lower threshold temperature has notbeen detected. In the event these LEDs are not illuminated, then asrepresented at line 1770 and block 1772 the practitioner is prompted topress the stop therapy button or switch 1604. As this occurs, asrepresented at line 1774 and block 1776, red LED 1606 is illuminatedand, as represented at line 1778, the procedure extends to node A whichreappears with line 1780 extending to line 1702. In the event of anaffirmative determination with respect to the query posed at block 1768,then the procedure continues as represented at line 1782 and block 1784.Timing for maximum warm-up interval commences and the procedurecontinues as represented at line 1786 and block 1788. At block 1788, thecontrol program queries as to whether the stop therapy button or switch1604 on the control console has been pressed. If it has been pressed,then as represented at line 1790 and block 1792 the heating unit isturned off; red LED 1598 is illuminated; and green LED 1600 is turnedoff. The procedure then, as represented at line 1794 and block 1796,determines whether therapy is to be resumed. In the event it is to beresumed, as represented at line 1800 and block 1802 the therapy may beresumed for the remaining duration of the maximum warm-up interval orunlapsed therapy time by actuating or pressing the start therapy buttonor switch 1596. This will cause a turning off of red LED 1598 and asrepresented at line 1802, the procedure reverts to node B. Node Breappears in FIG. 26E in conjunction with line 1804 extending to line1758. Where the determination at block 1798 is that the therapy is notto be resumed, then as represented at line 1806 and node 1808 thetherapy session is ended.

Returning to block 1788, where the stop therapy button or switch has notbeen pressed, then as represented at line 1810 and block 1812 adetermination is made as to whether all appropriate LEDs within array834 and array 844 are illuminated. In the event they are not, then asrepresented at line 1814 and block 1816 a determination is made as towhether the maximum time of warm-up has timed out. If the maximum timeof warm-up has timed out, then as represented at line 1818 and block1820, red LED 1598 is illuminated and as represented at line 1822 andblock 1824 an error message and prompt is presented at display 1588 andthe procedure advances to node C as represented at line 1826.

Looking momentarily to FIG. 261, node C reappears with line 1828extending to block 1830 which provides for the adjustment of the heatingunit output component position and/or the heating power level. Theprocedure then continues to node D as represented at line 1832. Node Dreappears in FIG. 26G with line 1834 extending to line 1810.

Returning to the query at block 1816, where the maximum time to warm-uphas not timed out, then as represented at line 1836 and block 1838 adetermination is made as to whether all appropriate LEDs within arrays838′ and 844′ are illuminated. In the event that they are not, then theprogram reverts to node D as represented at line 1840. Where those LEDsare appropriately illuminated, the program continues as represented atline 1842 extending to block 1844 providing for the commencement oftherapy time-out. Returning to the query at block 1812, where thecondition represented at block 1838 obtains, then the procedure divertsto line 1842 as represented at line 1846.

Returning to block 1844, where therapy time-out has commenced, then asrepresented at line 1848 and block 1850 where the heating unit electedis one requiring intermittent heating and interrogation, then that formof system activation is utilized in accordance with the interrogate/heatduty cycle elected in connection with up-down switches 1577 and readout1578. The procedure then continues as represented at line 1852 (FIG.26H) to the query posed at block 1854. Where any of the LEDs in thearray 848′ are illuminated, then as represented at line 1856, theprogram looks to node E. Looking momentarily to FIG. 26J, node Ereappears in conjunction with line 1858 extending to block 1860. Block1860 provides for turning off the heating unit, whereupon as representedat line 1862 and block 1864, the interrogation assembly is turned-onand, as represented at line 1866 the procedure reverts to node C (FIG.261).

Returning to the query at block 1854, where none of the temperatureexcursion LEDs at array 848 are illuminated, then the procedureprogresses as represented at line 1868 and block 1870. Block 1870determines whether or not the therapy duration has timed-out. In theevent that it has not, then as represented at loop line 1872 extendingto line 1852, the procedure dwells until such time-out occurs. At suchtime-out, as represented at line 1874 and block 1876 green LED 1602 isilluminated and green LED 1600 is turned off. As represented at line1878 and block 1880 the heating unit and interrogation assembly areturned off and, as represented at line 1882 and block 1884 therapy dataare recorded and as represented at line 1886 and node 1888 the therapysession is ended.

Hyperthermia currently is employed for purposes of limiting restenosisat the location of implanted stents in blood vessels. In general, suchstents, for example, may be utilized in percutaneous transluminalcoronary angioplasty (PTCA) for purposes of avoiding a collapse ofarteries subsequent to balloon implemented dilation. Thermal treatmentat the site of the stent will typically fall within a temperature rangefrom about 40° C. to about 45° C. As in other thermotherapeuticprocedures, necessary sensing of temperature heretofore has been carriedout in an invasive manner. Specifically, a transluminal catheter bornethermal sensor is maneuvered within the stent structure in the course ofthe thermal therapy procedure. As is apparent, such an invasivepositioning of the temperature sensor is required each time thehyperthermia therapy is performed, a procedure which may be called forrelatively often. In addition to the risk of this invasive positioningof the temperature sensor, the catheterization of the patient involves asubstantial cost. See the following publications in this regard:

-   -   (43) Stefanadis, C., et al., “Hyperthermia of Arterial Stent        Segments by Magnetic Force: A New Method to Eliminate Intimal        Hyperplasia.” Journal of the American College of Cardiology,        37 (2) Supp. A: 2A-3A (2001).    -   (44) See additionally European Patent Application No. EP        1036574A1.

FIGS. 27 and 28 illustrate an initial embodiment for a stent formed ofnon-magnetic material or material which can be heated from an extra bodysource, for example, by alternating current field heating and whichinitially incorporates an untethered temperature sensor which is fixedto it prior to the implantation. Looking to FIGS. 27 and 28, themesh-structured stent is represented generally at 1900 extending about acentral axis 1902. Typically, such stents as at 1900 are formed of anon-magnetic inductively exercisable material, for example, austeniticstainless steel such as type 316, titanium, titanium alloys and nitinol.Non-magnetic materials are utilized inasmuch as they often will belocated within the imaging field of highly magnetic devices such as MRIsystems and the like. Stent structures are described in the followingpublications:

-   -   (45) Interventional Vascular Product Guide, Martin Dunitz, Ltd.,        London (1999).    -   (46) Handbook of Coronary Stents, 3rd ed., Martin Dunitz, Ltd.,        London (2000).

The mesh-like generally cylindrically-shaped stent 1900 is seen to beimplanted such that its outwardly disposed contact surface 1904 willhave been urged into abutting and fixed intimate connection with theintima of a blood vessel 1906. Fixed to contact surface 1904 at thecentral region of stent 1900 is an untethered temperature responsiveassembly according to the invention which is represented generally at1908. Component 1908 is configured with the rod-shape of device 670described in connection with FIGS. 14 and 14A-14C. The ferrite core asdescribed at 672 of the component will be formulated to develop a Curietransition at an upper temperature limit as described above. That uppertemperature limit is elected inasmuch as the instant embodiment includesonly one passive device with a signature resonant center frequency.Sensor 1908 may be bonded with the stent 1900 and its securement may befurther assured by the positioning of a biocompatible flexible sheath orband 1910 over the central portion of the stent 1900 and over theoutwardly disposed surface 1912 of the sensor assembly 1908. Band 1910may, for instance, be formed of a biocompatible, non-metallic materialsuch as silicone elastomer, Dacron or Teflon. The arrangement is seen toslightly additionally distend blood vessel 1906 at region 1914. Ifdesired, the sensor assembly 1908 may be mounted in intimate thermalexchange relationship with the stent 1900. Providing a biocompatibleelectrically insulated conformal coating such as the earlier-describedParylene as shown at 1916 in FIG. 28 is beneficial and may promoteadhesion of the sensor 1908 to stent 1900.

The combined stent and untethered sensor components discussed inconjunction with FIGS. 27 and 28 also may be utilized to implement athermally activatable drug release feature. Referring to FIGS. 29 and30, a stent represented generally at 1920 with a centrally disposed axis1922 is shown having been implanted within a blood vessel 1924. Attachedto the outer contact surface 1926 of stent 1920 is an unteatheredpassive resonant circuit based sensor component 1928. Sensor component1928 may, as before, be configured as described in connection with FIGS.14 and 14A-14C. Component 1928 may be fixed in thermal exchangerelationship with the contact surface 1926 and further may be coatedwith an electrically insulated conformal biocompatible coating 1930 suchas the earlier-described “Parylene” which functions to aid in thesecurement of the sensor to the stent 1920. This securement is furtherenhanced by a flexible band or sheath 1932 surmounting both the stent1920 and the passive resonant sensor component 1928. Band 1932 may bestructured in the manner of earlier-described band 1910. Note, howeverwith the arrangement of FIGS. 29 and 30 that the inward surface 1934 ofstent 1920 is coated with a thermally activatable drug release coatingas shown at 1936. The release coating will have a thickness which mayfall within the range of about 0.001 inch (0.025 mm) to about 0.20 inch(5.0 mm) and preferably will fall within a range of from about 0.005inch (0.13 mm) to about 0.10 inch (2.5 mm). Such drugs may be provided,for example, as paclitaxel and the antibiotic Sirolimus as well asanti-thrombogenic agents such as heparin and the like. See the followingpublications in this regard:

-   -   (47) Simonsen, “Percutaneous intervention arena still expanding        for heart disease.” Cardiovascular Device Update 7(5): 1-7 (May        2001).    -   (48) “Drug-Coated Stents Poised for Growth”, Cardiovascular        Device Update, 7(9): 8-10 (September, 2001).

The nominal drug release temperature will range from about 39° C. toabout 65° C. and preferably from about 41° C. to about 50° C. Drugrelease coating 1936, when non-invasively heated to a drug releasingtemperature, provides a controlled amount of a selected drug at thesitus of the stent 1920 to limit restenosis phenomena. Such a drugrelease process can be repeated at therapeutic intervals which may rangefrom weeks to months to even years. Additionally, the coating may beactivated in the event the patient's symptoms or diagnostic methodsindicate that restenosis is occurring and progressing to the point thattherapeutic intervention is warranted. Where hyperthermia therapy iscombined with drug release activity, more than one passive resonantfrequency based sensor may be employed each being assigned a differentCurie transition temperature.

The untethered passive resonant circuit based sensors preferably arepositioned on the outer contact surface of the stent structure, inasmuchas such location provides a factor of safety with respect to theadhesion of the individual components to that contact surface. Shouldthe coupling be damaged, the sensor components are retained by the stentstructure itself outside of luminal blood flow. In addition, thedetectable signal amplitude issuing from the passive resonant circuit isgreater if the sensor is placed on the outside of a metallic stent.

Two of these resonant circuit based passive sensors may be employed toprovide the earlier-described lower threshold temperature sensing andupper limit temperature sensing. Additionally, multiple sensors may beemployed to provide a redundancy. FIGS. 31 and 32 illustrate a stentstructure with lower threshold and upper limit temperature value sensorsin conjunction with a nonmagnetic stent represented generally at 1940.Formed, as before, of a nonmagnetic material, stent 1940 is seendisposed about a central axis 1942 and has a generally mesh-likestructuring with an outwardly disposed contact surface 1944 of generallycylindrical configuration. Untethered passive resonant circuit basedlower threshold and upper limit temperature level sensors are shownrespectively at 1946 and 1948 coupled to contact surface 1944 atdiametrically opposite locations. As before, each of these sensors maybe configured in the manner described in connection with FIGS. 14 and14A-14C. The assembly additionally may be coated with an electricallyinsulative biocompatible material represented at 1950 in FIG. 32. Thatmaterial, which may be the earlier described “Parylene” functions toenhance the bond between the sensors and the outer contact surface 1944.Sensors 1946 and 1948 further are secured to the contact surface 1944 bya flexible band or sheath 1952. Band 1952 is structured in the manner ofthe earlier-described band 1910. As before, the instant figures revealthat the blood vessel 1954 within which stent 1940 is positioned isdiametrically enlarged at regions 1956 and 1958 to accommodate for thethickness of sensors 1946 and 1948 as well as band 1952.

As noted earlier, essentially all metallic stents which have beenimplanted are formed of nonmagnetic material in view of the potentialinvolvement of highly magnetic imaging systems. As a consequence, thosepre-implanted stents can be retrofitted in vivo with the temperaturesensing aspect of the present invention to enhance noninvasivethermotherapeutic procedures or subsequent treatment of restenosisphenomena. The retrofitting approach, in effect, provides for theinstallation of a temperature sensing component containing a stent-likestructure which is diametrically expandable within the preexistingstent.

Referring to FIGS. 33 and 34, an asymmetrical retrofitting design isillustrated. In the figure, a nonmagnetic metal mesh stent isrepresented in general at 1962 disposed about a central axis 1964 whichhas been previously implanted within a blood vessel 1966. Note in thisregard that the outwardly disposed surface 1968 of the stent 1962 is incontact with the intima of the vessel 1966. The untethered passiveresonant circuit based temperature sensor carrying insert or supportmember is seen at 1970 disposed about central axis 1964. Insert 1970 isof generally cylindrical configuration with an interior surface 1972 andexterior surface 1974 to which an untethered passive resonant circuitbased temperature sensor 1976 is bonded. That bond may establish atemperature exchange relationship between the insert and the stent. Ingeneral, the insert 1970 may be formed with essentially the same meshstructuring and material as present in the previously implanted stent1962. Such mesh structuring is not shown in the figures in the interestof illustrational clarity. FIG. 34 shows that the insert and associatedsensor is coated with a biocompatible coating 1978 which may be providedas the earlier-described “Parylene” material. Additionally, thestructural integrity of the attachment of the sensor 1976 is enhanced bya flexible band 1980. Sensor carrying insert or support member 1970 isinserted within the preexisting stent 1962 using balloon angioplastyprocedures. In order to accommodate for the asymmetrical positioning ofonly a single sensor 1976, the insert member 1970 is structured so thatit is preferentially expandable in the region 1982 immediately beneaththe sensor 1976. Accordingly, upon balloon expansion during theplacement of insert 1970, the region 1982 will expand from an initialinsertion diameter diametrically outwardly against the interior surface1984 of the preexisting stent 1962 to create the crimping expansion ofthe contacting surface of that stent 1962 as represented at region 1982.Preferential expansion of the insert 1970 can be provided by structuringthe stent to be thinner at that region and/or the mesh structure openingsize may be asymmetrically varying.

Referring to FIGS. 35 and 36, a retrofitting or “stent within a stent”approach is illustrated wherein two passive, resonant frequency basedtemperature sensors are employed. One such sensor may be structured witha core component providing a lower threshold Curie temperature and theother an upper limit Curie temperature as above-described. With such anarrangement, the temperature elevation at the stent may be bracketedbetween those two temperature values. In the figures, a pre-implantednonmagnetic stent is represented generally at 2000. As before, stent2000 has a mesh-type structure of generally cylindrical configurationdisposed about central axis 2002. The cylindrical outer surface 2004 ofstent 2000 is in abutting compressive engagement with the intima of ablood vessel 2006. In order to carry out a hyperthermia form oftreatment for restenosis with the necessary temperature control, asecondary stent or support member insert represented generally at 2008extending about axis 2002 is formed of an expandable mesh material,e.g., stainless steel 316, Nitina, or titanium, and functions to supportdiametrically oppositely disposed temperature sensors configuredaccording to the invention and represented generally at 2010 and 2012.Sensor 2010 may be configured with a ferrite core component having aCurie temperature selected as a lower threshold temperature, whilesensor 2012 may be configured with a ferrite core component exhibitingan upper limit Curie temperature to effect a noted bracketing control.Similar to the embodiment of FIGS. 33 and 34, the insert or supportmember 2008 is configured with a cylindrical wall surface 2014 and anexterior surface 2016 upon which the sensors 2010 and 2012 areconnected. To enhance this connection, a flexible band 2018 surmountsboth the cylindrical exterior wall surface 2016 and the sensors 2010 and2012. FIG. 36 reveals that the insert and associated sensors are coatedwith an electrically insulative biocompatible conformal coating 2020such as the earlier-described “Parylene”. Insert 2008 also may bestructured so that it is preferentially expandable in the region of eachof the sensors 2010 and 2012. Upon balloon expansion during theplacement of the insert and its supported sensors the regions 2022 and2024 will expand from an initial insertion diameter diametricallyoutwardly against the interior surface 2026 of the preexisting stent2000 to create the crimping expansion of the contacting surfaces.Preferential expansion at those regions can be provided as described inconjunction with FIGS. 33 and 34. The earlier-discussed hyperthermiatherapy temperature ranges apply to the arrangement of FIGS. 35 and 36.A nominal stent heating temperature of 45° C. has been described inpublication (44) supra.

See additionally the following publication:

-   -   (49) Thury, A., et al., “Initial Experience With Intravascular        Sonotherapy For Prevention Of In-Stent Restenosis; Safety And        Feasibility”, J. of Am. College of Cardiology 37 (2)        Supplement A. (2000)

The instrumentation described in connection with FIGS. 19 and 25 ingeneral may be employed for carrying out the heating of nonmagneticstents as described above. Where inductive heating components areutilized then the intermittent form of operation of the system is calledfor. However, U.S. Pat. No. 6,451,044 (supra) describes an ultrasoundheating of a stent formed of an ultrasound absorptive material. Such astent therefore could be heated while continuous temperature monitoringis carried out. Looking to FIG. 37, the instrumentation and supportequipment discussed in connection with FIG. 25 are illustrated forexemplary purposes in connection with a patient 2030. Patient supportcomponents, heating components and interrogation components which arerepeated from FIG. 25 are shown with the same earlier presentednumerical identification but in primed fashion. Stent 1940 (FIG. 31)reappears adjacent the heart region 2032 of patient 2030. Heatingcomponent 1557 is located in adjacency with the stent 1940. Excitationcoil 1530′ is located for exciting the temperature sensors of stent1940, while the sense antenna 1542′ is positioned about the region ofthe stent 1940 location. The instantaneous heating power generatedwithin the stent 1940 will generally fall with a range of from 0.20calories/second to about 20 calories/second and preferably will bewithin a range of between about 0.5 calories/second and about 10calories/second. The nominal hyperthermia therapy temperature for stentssuch as at 1940 will fall within a range of from about 39° C. to about70° C. and preferably within a range from about 41° C. to about 50° C.

Referring to FIGS. 38A-38B and 39A-39H a procedural flow chart ispresented concerning the implanting of stent supported temperaturesensors according to the invention. The procedure is associated with theinstrumentation and equipment described in connection with FIG. 37 andcommences with start node 2040 and line 2042 extending to block 2044.Block 2044 describes the provision of a stent with two or more sensors,one having an inductor core exhibiting a lower threshold Curietemperature and the other having an inductor core exhibiting an upperlimit Curie temperature characteristic such that they bracket atemperature range for hyperthermia treatment of stenosis/restenosis. Asrepresented at line 2046 and block 2048, as an alternative, a supportinsert as described in connection with FIGS. 35 and 36 may be providedhaving the same form of sensor response characteristic. The procedurethen continues as represented at line 2050 and block 2052 providing forthe loading of all unique resonant frequencies into the interrogationassembly. Identification of the sensors is only required where more thantwo are at hand. Next, as represented at line 2054 and block 2056 theinterrogation assembly is utilized to carry out an ex-vivo pre-testingof the two sensors for their resonant performance at room temperature.Accordingly, as represented at line 2058 and block 2060, a query isposed as to whether the appropriate LEDs from arrays 834′ and 844′ areilluminated. In the event that they are not, then as represented at line2062 the procedure extends to node A. Node A reappears with line 2064extending to start line 2042. Where all appropriate LEDs have beenilluminated, then as represented at line 2066 and block 2068 (FIG. 38B)a general or local anesthetic agent is administered and, as representedat line 2070 and block 2072 the sensor containing stent is locatedwithin the patient's blood vessel using conventional stent deliverysystems. Once it is positioned, it is deployed at the target locationand the deployment system is removed. As an alternative, as representedat line 2074 and block 2076 a support member with two associated sensorsaccording to the invention is described in conjunction with FIGS. 35 and36 may be positioned within a previously implanted stent and expandedsuch that it is secured within that preexisting stent. The deploymentsystem then is removed. The procedure then continues as represented atline 2078 and block 2080 providing for the positioning of a marker onthe skin surface of the patient close to the location of the stent.Next, as represented at line 2082 and block 2084 the location of thethus placed marker is recorded for future reference and the two resonantcenter frequencies are recorded for any future reference. As representedat line 2086 and node 2088 the stent positioning phase is then ended.

Subsequent to the stent positioning phase, the patient will be monitoredfor the occurrence of clinically significant stenosis/restenosis. Thismay be to a requirement for a number of hyperthermia based treatmentsessions which can extend over a lengthy period. Referring to FIGS.39A-39H, and block 2090 of FIG. 39A, such checks may be carried out, forinstance, using angiography, diagnostic ultrasound, ex-ray, or MRItechniques. The procedure then continues as represented at line 2092 andblock 2094 presenting a query as to whether or not evidence ofstenosis/restenosis is present. In the event that it is not, then asrepresented at line 2096 and block 2098 such checks are continued, thepatient's cardiac circulatory function being monitored on a periodicbasis. Where evidence of stenosis/restenosis does exist, then asrepresented at lines 2100 and 2101, thermal therapy according to theinvention is commenced. Lines 2100 and 2101 are labeled inasmuch as asequence of such sessions may be carried out over an extended intervalof time. Accordingly, certain of the steps undertaken earlier may haveto be repeated. Line 2101 is seen extending to block 2102 providing forthe election of a stent heating system. Next, as represented at line2104 and block 2106 the practitioner elects the initial heating powerlevel for the heating system and, as represented at line 2108 and block2110 determines the maximum warm-up interval, t_(wu) to initiallyachieve the lower threshold designated temperature. Additionally, asrepresented at line 2112 and block 2114 a determination is made as tothe session therapy duration at temperatures at or above the designatedlower threshold temperature and below the upper limit temperature. Asrepresented at line 2116 and block 2118 the marker at the patient's skinmay be relocated at its earlier recorded position if necessary. With themarker available, as represented at line 2120 and block 2122 the patientis positioned on an appropriate treatment support such that the markeris clearly visible to provide for close proximity of the heating systemoutput, for instance, an inductive coil. Thus, as represented at line2124 and block 2126 the heating system output component is placed asclose as practical to the stent with guidance by the marker. Theprocedure then continues as represented at line 2128 and block 2130(FIG. 39B) providing for again utilizing the marker to positionexcitation and receiver or sense antennae as close as practical to thestent. It may be recalled that the sense antenna is quite flexible andmay be draped over the patient's body in the vicinity of the stent.Next, the control system is activated as represented at line 2132 andblock 2134, and, as represented at line 2136 and block 2138, wherenecessary the unique resonant frequencies and, if called for, sensoridentifiers are loaded into the interrogation assembly control function.As represented at line 2140 and block 2142 a selection is made as to theinterrogate/heat duty cycle which may be provided as part of themanufacturer of the system or inputted at up-down switches 1577′ seen inFIG. 37. As represented at line 2144 and block 2146, the practitionerwill actuate or press the therapy time elapsed reset switch or buttonshown in FIG. 37 at 1586′. The procedure then continues as representedat line 2148 and block 2150 providing for testing the interrogationassembly acquiring on and continuity type status information. Theinformation thus acquired, as represented at line 2152 and block 2154(FIG. 39C), a determination is made as to whether the status of theinterrogation assembly is ok. In the event that it is not, then asrepresented at line 2156 and block 2158 an error message is presented atdisplay 1588′ and, as represented at line 2160 and block 2162, a promptis displayed advising the practitioner to check cable attachments,whereupon the procedure reverts to line 2152 as represented at line2164. Where the determination at block 2154 is that the interrogationassembly status is ok, then as represented at line 2166 and block 2168,green LED 1582′ (FIG. 37) is illuminated and the procedure attends tothe testing of the stent heating unit as represented at line 2170 andblock 2172. Upon actuating the heating unit into an on condition, asrepresented at line 2174 and block 2176 the on continuity status of theheating unit is acquired and, as represented at line 2178 and block 2180a determination is made as to whether the heating unit status is ok. Inthe event that it is not, then as represented at line 2182 and block2184 an error message is presented at display 1588′ (FIG. 37).Additionally, as represented at line 2186 and block 2188, a promptmessage advising the practitioner to check lead/cable attachment isprovided at that display. The procedure then reverts to line 2174 asrepresented at line 2190.

Where the heating unit status is ok, then as represented at line 2192and block 2194, green LED 1590′ (FIG. 37) is illuminated and theprocedure continues as represented at line 2196 and block 2198.Hyperthermia therapy is started by actuating the start therapy switch1596′. Actuating the start therapy button, in turn, effects theillumination of green LED 1600′ as represented at line 2200 and block2202 (FIG. 39D). Next, as represented at line 2204 and block 2206, acheck is made that the appropriate LEDs located within arrays 834′ and844′ are illuminated inasmuch as they are at monitor temperatures. Forthe instant demonstration one LED in each of these arrays will beilluminated. In the event of a negative determination with respect tothe query posed at block 2206, then as represented at line 2208 andblock 2210 the practitioner will actuate the stop therapy switch 1604′and, as represented at line 2212 and block 2214, red LED 1606′ isilluminated and the green LED 1500′ is turned off. The procedure thendiverts as represented at line 2216 to node A. Node A reappears in FIG.39B in connection with line 2218 extending to line 2128.

Where the query at block 2206 indicates that the appropriate LEDs areilluminated, then as represented at line 2220 and block 2222 the controlsystem commences timing for the maximum time to warm up. As representedat line 2224 and block 2226 a determination is made as to whether thestop therapy switch or button 1604′ (FIG. 37) has been pressed oractuated. In the event that it has, then as represented at line 2230 andblock 2232 the heating unit is turned off, red LED 1598 is illuminatedand green LED 1598′ is illuminated and green 1600′ is turned off (FIG.37). Next, as represented at line 2234 and block 2236 the practitionerdetermines whether or not therapy is to be resumed. If it is to beresumed, as represented at line 2238 and block 2240 the start therapyswitch or button 1596′ is actuated and red LED 1598′ is turned off (FIG.37). The procedure then reverts to node B as represented at line 2242.Node B reappears at FIG. 39C in conjunction with line 2246 extending toline 2196. Where the determination at block 2236 is that therapy is notto be resumed, then as represented at line 2241 and node 2243 thetherapy session is ended.

Returning to FIG. 39D and block 2226, where the stop therapy switch hasnot been actuated, then as represented at line 2248 and block 2250 (FIG.39E), a determination is made as to whether appropriate ones of the LEDsin array 838′ and array 844′ are illuminated. Where they are not, asrepresented at line 2252 and block 2254 a determination is made as towhether the maximum time to warm-up interval has timed out. In the eventthat it has, then as represented at line 2256 and block 2258, red LED1598′ is illuminated and, as represented at line 2260 and block 2262error and prompt messages are provided at display 1588′ and theprocedure reverts to node C as represented at line 2264.

Looking momentarily to FIG. 39G, node C reappears in conjunction withline 2266 extending to block 2268. Block 2268 provides for adjusting theheating unit output component position and/or the heating power level.The procedure then reverts as represented at line 2270 to node D.

Returning to FIG. 39E, node D reappears in association with line 2272extending to line 2248. Where the inquiry posed at block 2254 indicatesthat the maximum warm-up time interval has not timed out, then asrepresented at line 2274 and block 2276 the query as posed at block 2250is repeated in a determination as to whether therapy level temperatureshave been reached. In the event that they have not been so reached, thenas represented at line 2278, the procedure reverts to earlier describednode D. Where all appropriate ones of the LEDs are illuminated theprocedure continues as represented at line 2280. Correspondingly, wherethe same result is achieved with respect to the query at block 2250,then the procedure continues as represented at line 2282 extending toline 2280. Line 2280, in turn, extends to block 2284 indicating thecommencement of session therapy time-out with a resulting activation oftherapy time elapsed readout 1584′ (FIG. 37). During this therapy time,as represented at line 2286 and block 2288, for intermittent performancewhich typically is employed with stent therapy, the heating unit andinterrogation assembly are intermitted or cycled in accordance with theduty cycle which may have been provided in conjunction with up-downswitches 1577′. The procedure then continues as represented at line 2290and block 2292 (FIG. 39F) where a query is posed as to whether an LED inthe over-temperature array 848′ is illuminated. In the event that thereis such an over-temperature, as represented at line 2294 the procedurediverts to node E.

Looking momentarily to FIG. 39H, node E reappears with line 2296extending to block 2298 providing for turning off the heating unit.Then, as represented at line 2300 and block 2302 the interrogationassembly is turned on and as represented at line 2304, the procedurereverts to earlier-described node C which ultimately returns to node D.

Returning to FIG. 39F and block 2292, where no temperature excursionsare at hand, then as represented at line 2306 and block 2308 adetermination is made as to whether the therapy duration has timed out.If it has not, the procedure dwells as represented by loop line 2310extending to line 2290. Where no temperature excursions are at hand,then the procedure continues as represented at line 2312 and block 2314to carry out the illumination of green LED 1602′ and turn off green LED1600′ (FIG. 37). Further, as represented at line 2316 and block 2318 theheating unit and interrogation assembly are turned off and, asrepresented at line 2320 and block 2322 the therapy data are recorded.Upon completing a recordation of the therapy data, as represented atline 2324 and node 2326 the therapy session is ended.

The passive resonant circuit based sensor implant of the invention alsomay be implemented utilizing an inductive component exhibitingsubstantially uniform relative permeability over a temperature range ofinterest, for example, between 40° C. and 45° C. in combination with acapacitor component which exhibits capacitance values as a function oftemperature. The involved passive resonant circuit will physicallyappear essentially identical to that described in connection with FIGS.7 and 14 and 14A-C. Looking to FIG. 40, an inductor is representedgenerally at 2340 as comprising a ferrite core 2342 about which areprovided the turns 2344 of an inductive winding. These turns 2344 arecoupled in series, as represented at leads 2346 and 2348, to theoppositely disposed plates of a capacitor 2350, the capacitance valuesof which vary with temperature. In this regard, referring to FIG. 41 thecapacitance exhibited by capacitor 2350 may be represented by the curve2354 as it extends between capacitance values C1 and C2 within a rangeof temperatures, for example, between 40° C. and 45° C. The value ofcapacitance is given by the expression:C=(const.)(∈A)/d

-   -   where: C is capacitance;    -   ∈ is the dielectric constant;    -   A is plate area; and    -   d is the distance between the capacitor plates.

From that expression it may be seen that the capacitance may be variedby altering either or both the values d and ∈.

Looking additionally to FIG. 42, curve 2354 is reproduced in conjunctionwith the relative permeability characteristic of the core 2342 asrepresented at curve 2352. For exemplary purposes, curve 2352 is shownexhibiting a Curie transition at knee region 2356 which may be, forexample, 100° C., a temperature level well above the temperature rangeof interest eliciting the variation in capacitance with temperature.This implant arrangement is not limited therefore to a single Curietemperature based set point but may provide monitorable resonantfrequencies which vary along the curve 2354 since the resonantfrequency, f₀, is inversely proportional to the capacitance, C, asdiscussed earlier.

Since certain changes may be made in the above-described system,apparatus and method without departing from the scope of the inventionherein involved, it is intended that all matter contained in the abovedescription or shown in the accompanying drawings shall be intrepid asillustrative and not in a limiting sense.

1. A temperature responsive untethered sensor implant for evaluating atemperature rise from a monitoring temperature or temperatures to a setpoint temperature comprising: a core component exhibiting a relativepermeability characteristic elevating in value with a correspondingelevation in monitoring temperatures and exhibiting a Curie temperatureabove said monitoring temperatures corresponding with said set pointtemperature; an inductive winding with turns wound about said corecomponent to define an inductive component; a capacitor coupled withsaid inductive winding to define a resonant circuit electromagneticallyexcitable to have a resonating output at a select resonant centerfrequency and exhibiting a decrease in the intensity of said resonatingoutput at said select resonant center frequency when at temperaturesapproaching at said Curie temperature.
 2. The implant of claim 1 inwhich said implant further comprises: a non-magnetic heater componentcoupled in heat influencing relationship with said sensor implant at alocation substantially non-interfering with said resonating output. 3.The implant of claim 1 in which: said defined resonant circuit exhibitsan absence of said resonating output at said select resonant centerfrequency when at said Curie temperature.
 4. The implant of claim 1 inwhich: said core component is formed of ferrite material.
 5. The implantof claim 1 in which: said select resonant center frequency correspondsat least in part with the number of said turns of said inductivewinding.
 6. The implant of claim 1 in which: said select resonant centerfrequency corresponds at least in part with the value of capacitance ofsaid capacitor.
 7. The implant of claim 1 in which: said select centerfrequency corresponds with both the number of said turns of saidinductive winding and with the value of capacitance of said capacitor.8. The implant of claim 1 in which: said core component has an outersurface and extends along a component axis between oppositely disposedend surfaces; further comprising a first electrically insulative sleevehaving a first sleeve outer surface and located over said core componentouter surface and having oppositely disposed first sleeve ends extendingbetween or beyond said core component end surfaces; and said inductivewinding turns are wound over said sleeve outer surface.
 9. The implantof claim 8 in which: a second electrically insulative sleeve having asecond sleeve outer surface located over said inductive winding, havingoppositely disposed second sleeve ends extending beyond said firstsleeve ends.
 10. The implant of claim 9 in which: said capacitor ismounted within said second sleeve between a said first sleeve end and anadjacent said second sleeve end.
 11. The implant of claim 10 in which:said first and second sleeves are formed of polymeric material; and saidsecond sleeve is potted with a biocompatible epoxy adhesive.
 12. Theimplant of claim 10 in which said second sleeve, when potted, is coatedwith an electrically insulative biocompatible conformal layer.
 13. Theimplant of claim 10 in which: said second sleeve is potted with saidbiocompatible epoxy adhesive wherein the outwardly disposed surface ofsaid epoxy adhesive is disposed inwardly from at least one of saidsecond sleeve ends to define an anchoring structure for engagement withanimal tissue.
 14. The implant of claim 10 further comprising: abiocompatible anchor structure configured for engagement with animaltissue mounted within and extending from at least one of said secondsleeve ends.
 15. The implant of claim 9 in which said implant furthercomprises: a non-magnetic heater component coupled in heat influencingrelationship with said sensor implant at a said second sleeve end. 16.The implant of claim 15 in which: said heater component is configured asan open ended sleeve coupled at the said second sleeve outer surface.17. The implant of claim 1 in which said implant further comprises: athermally activatable release agent supported by said implant andeffective to disperse when said implant is within tissue at or belowsaid transition temperature.
 18. The implant of claim 1 in which: saidmonitoring and said set point temperatures are between about 39° C. andabout 70° C.
 19. The implant of claim 1 in which: said monitoring andsaid set point temperatures are between about 41° C. and about 50° C.20. The implant of claim 1 in which: said monitoring and said set pointtemperatures are between about 42° C. and about 45° C.
 21. The implantof claim 1 in which: said set point temperature is within a range fromabout 4° C. to about 13° C. over normal body temperature.
 22. The systemof claim 1 in which: said set point temperature is within a range fromabout 2° C. to about 33° C. over normal body temperature.